To understand ABV better, we began an epidemiological study of ABV in Japan. First, we collected blood samples from three birds: a Nymphicus hollandicus with clinically suspected PDD, an Eclectus roratus with FPD and a healthy duck (Anas platyrhynchos). We isolated total RNA from whole blood using TRIzol reagent (Invitrogen, Carlsbad, CA, USA), and reverse-transcribed with transcriptor reverse-transcriptase and random hexamer (Roche, Indianapolis, IN, USA). We designed degenerate primers based on the alignment of amino Talazoparib manufacturer acid

sequences of the N of ABV genotypes 1 to 5 (ABV1–5) and L of ABV genotypes 1 to 4 (ABV1–4) for detection of ABV-specific nucleic acid (Table 1). In this study, we used six primer pairs (MH168–176, 169–176, 173–176, 174–176, 175–170 and 175–177) and two primer pairs (MH171–172 and 178–179) for ABV N and L, respectively. We carried out PCR with Ex-Taq Hot Start Version (TaKaRa, Shiga, Japan) and eight pairs of degenerate primers using the following program: denaturation for 2 min, 10 cycles of 94°C for 30 s, 60–55°C

(the Osimertinib annealing temperature was decreased by 0.5°C every other cycle) for 30 s, 72°C for 30 s and 30 cycles of 94°C for 30 s, 55°C for 30 s, 72°C for 30 s followed by 72°C 3 min. Surprisingly, using degenerate primers for ABV N, we obtained bands of the expected sizes from the sample of the bird affected by FPD, but from the samples of the bird with PDD and the healthy duck. (Fig. 1a). On the other hand, using Methocarbamol primers for ABV L, we found no amplification of the expected bands in any of the samples (data not shown). The representative nucleic acid sequence of the amplicons (Acc. No. AB519142) showed 99% and 98% identity to two known ABV5 N sequences (Acc. No. FJ002318 and FJ002319) by BLAST and clustered into ABV5 according to phylogenetic analysis (data not shown). Furthermore, to confirm the above result, we carried out PCR with primers specific for the ABV5 M gene (MH180 and

181). An amplicon was generated as expected (Fig. 1b) and its nucleotide sequence (Acc. No. AB519143) showed 98% and 95% identity to two previously identified ABV5 M sequences (Acc. No. FJ002334 and FJ002335). These results indicated that the FPD-affected bird may have been infected with genotype 5 of ABV. We also tested the FPD bird’s blood for beak and feather disease virus (circovirus) and budgerigar fledgling disease virus (polyomavirus) by PCR, and found that it was negative for both viruses (data not shown). After 8 months of blood sampling, we collected feces from the ABV5 (+) bird and a healthy bird of the same species. At that time, the ABV5 (+) bird showed clinical signs of FPD but not of PDD. We suspended the fecal samples in PBS and centrifuged at 9,500 ×g for 10 min at 4°C. We isolated RNA from the supernatant using a viral RNA mini kit (Qiagen, Tokyo, Japan), and subjected it to RT-PCR with random hexamers and the MH175–170 primer pair.

© 2012 Wiley Periodicals, Inc. Microsurgery,

2012. “
“Nicotine causes ischemia and necrosis of skin flaps. Phosphodiesterase-5 (PDE-5) inhibition enhances blood flow and vasculogenesis. This study examines skin flap survival in rats exposed to nicotine that are treated with and without PDE-5 inhibition. Eighty six rats were divided into five groups. Group 1 received saline subcutaneous (SC) once per day. Group 2 received nicotine SC 2 mg/kg day. Group 3 received sildenafil 3-MA nmr intraperitoneal (IP) 10 mg/kg day. Group 4 received nicotine SC 2 mg/kg and sildenafil IP 10 mg/kg day. Group 5 received nicotine SC 2 mg/kg day and sildenafil IP 10 mg/kg two times daily. After 28 days of treatment, modified McFarlane flaps were created, silicone sheets were interposed, and flaps were sutured. Photographs were taken on postoperative days 1, 3, and 7 and fluorescence angiography was used on day 7, both to evaluate for skin flap necrosis.

Rats were euthanized and flaps were harvested for Vascular Endothelial Growth Factor (VEGF) Western blot analysis. selleck compound Images were analyzed by three blinded observers using ImageJ, and necrotic indices were calculated. The nicotine and PDE-5 inhibition twice-daily group showed a 46% reduction in flap necrosis when compared to saline only (P < 0.05) and a 54% reduction when compared to nicotine only (P < 0.01). Fluorescence angiographic image Farnesyltransferase analysis revealed reductions in flap necrosis (P < 0.01). VEGF analysis trended toward increased VEGF for all sildenafil-treated groups (P > 0.05). PDE-5 inhibition exhibits a dose-dependent reduction in skin flap necrosis in rats exposed to nicotine. This suggests that PDE-5 inhibition may mitigate the ill effects of smoking on skin flaps. © 2014 Wiley Periodicals, Inc. Microsurgery 34:390–397, 2014. “
“Nerve regeneration after surgical reconstruction is far from optimal,

and thus effective strategies for improving the outcome of nerve repair are being sought. In this experiment, we verified if postoperative intraperitoneal melatonin (MLT) administration after intraoperative platelet gel application improves peripheral nerve regeneration. In adult male rats, 1-cm long sciatic nerve defects were repaired using four different strategies: autologous nerve graft repair followed by MLT (NM, n = 5), collagen conduit repair followed by MLT (CM, n = 5), platelet gel-enriched collagen conduit repair followed by MLT (CGM, n = 6), and platelet gel-enriched collagen conduit (CG, n = 5) repair followed by no substance administration. Sham operated animals were used as controls (Cont, n = 5). Ninety days after surgery, the nerve regeneration outcome was comparatively assessed by means of electrophysiological and stereological analysis. Electrophysiology revealed no significant differences between the experimental and the sham control groups.

The authors do so by demonstrating differences in Blimp-1 expression between T lymphocytes isolated from patients with chronic active HIV versus those from long-term nonprogressors and showing that this is matched by differences in the cells’ capacity to produce IL-2 and the level of expression of the inhibitory receptor PD-1.

The data presented here suggest that this may relate to differential regulation of Blimp-1 by the micro RNA, mIR-9. These findings complement current murine work and fit squarely within the research priorities, as outlined by the International AIDS Society, for determining a cure for AIDS. The International AIDS Society Scientific Working Group on HIV Cure promoted seven key research goals, including the need to ‘determine host mechanisms that control HIV replication in ABT-737 datasheet the absence of therapy’ [1]. This research goal hinges on the fact that HIV infection affects humans in a heterogeneous manner. In most individuals, primary inoculation

is followed by rapid viral replication leading to a high viral load, measured as levels of virus detectable in the blood. Following the development of the adaptive immune response the viral load decreases. In the majority of individuals, in the absence of therapy, this is followed by a finite period, termed asymptomatic HIV infection, during which the viral load remains detectable and is accompanied by a steady decrease in the CD4+ T-cell numbers of the host. The CD4+ cell count shows all an inexorable fall and eventually crosses a critical threshold beyond which the patient suffers the clinical features of defective cell-mediated immunity, click here culminating in AIDS. For certain individuals, this usual disease progression differs favorably. In those termed long-term nonprogressors (LNTPs), following primary infection the viral load is unusually reduced and

the loss of CD4+ T cells occurs at a vastly diminished rate. These individuals, although initially thought to show no disease progression, are in fact now known to be at risk of disease progression although developing with greatly reduced kinetics [2]. The recommendation from the International AIDS society is, therefore, that we seek to understand how HIV replication is controlled in this patient group in order to reach an understanding of how to modulate immunity to better control HIV infection for all patients. The host control of viral infection depends on the T-cell adaptive immune response and this response differs between those with progressive chronic HIV infection (CHI) and termed long-term nonprogressors. The T cells from individuals with CHI have significantly fewer polyfunctional T cells (i.e. T cells that secrete multiple cytokines), and these cells express higher numbers and levels of inhibitory receptors such as PD-1 and CTLA-4 [3]. This T-cell phenotype of expression of inhibitory receptors and diminished ability to secrete cytokines has been termed T-cell ‘exhaustion’.

2A and B). Analysis of the CD21/CD23 profile of

E-Btk-2 Tg splenic B cells revealed an apparently Z-IETD-FMK clinical trial normal population of CD21−CD23− immature B cells, but the follicular B cells were significantly reduced in number and manifested low surface expression of both CD21 and CD23 (Fig. 2A and B). CD21highCD23low MZ B cells were completely lacking in E-Btk-2 mice. As Btk-deficient B cells appear to have slightly increased CD21 expression levels (Fig. 2A), it was conceivable that in E-Btk-2 mice MZ B cells were still present but lacked CD21 expression. However, almost complete absence of MZ B cells in the spleen of E-Btk-2 mice was confirmed both by CD1d FACS staining (Supporting Information. Fig. S1) and by immunohistochemical analysis that demonstrated the absence of IgM+ B cells outside the rim of MOMA-1+ metallophilic macrophages (Fig. 5B, left panels). In contrast, EY-Btk-5 Tg mice had significantly reduced numbers of follicular B cells and apparently normal numbers of immature B cells. Due to CDK inhibitor review the reduction in follicular B cells, relative proportions of MZ cells were increased (Fig. 2A), but their absolute numbers were in the normal range (Fig. 2B). The milder phenotype in EY-Btk-5 Tg mice,

as compared with E-Btk-2 transgenic mice might originate from differential effects of the E41K single and the E41K-Y223F double mutation or alternatively from the ∼2 times higher expression levels of the E-Btk-2 mutant, as compared with EY-Btk-5. To investigate this, we generated mice homozygous for the EY-Btk-5 Tg and analyzed the B-cell compartment by flow cytometry. Strikingly, homozygous EY-Btk-5 mice manifested a phenotype reminiscent of that found in E-Btk-2 mice, with severely reduced numbers of B cells, a complete lack of CD21highCD23low MZ B cells and a significant reduction in the numbers of follicular B cells, whereby residual B cells were CD21lowCD23low (Fig. 2C). Taken together, these findings show

that expression of constitutive active Btk significantly affected B-cell differentiation beyond the transitional B-cell stage, resulting in reduced numbers of follicular B cells and the absence of MZ B cells in E-Btk-2 Tg mice and in homozygous EY-Btk-5 Tg mice. Because mutant mice with enhanced BCR signaling often show increased numbers of B-1 B cells 12–19, we evaluated oxyclozanide the expression of the B-1-associated surface markers CD5 and CD43 in spleen, MLN and peritoneal cavity. We identified significant proportions of B220lowCD5+CD43+ B-1 B cells in the spleens of E-Btk-2 and EY-Btk-5 mice, in contrast to spleens of WT and Btk-deficient mice, which contained only minor fractions of B-1 cells or completely lacked B-1 cells, respectively (Fig. 3A and B). In MLN of both E-Btk-2 and EY-Btk-5 mice, the proportions of B cells were significantly reduced, whereby B220lowCD5+CD43+ B-1 B cells, which are normally not present in MLN (Supporting Information Fig. S2A), were prominent.

Interestingly, the marked differences between WT and CD68TGF-βDNRII mice were primarily associated with the resolution of colitic inflammation. Impairment of TGF-β responsiveness in Mϕs delayed the reduction of granulocytic inflammation, impaired IL-10 release, but increased the production of IL-33, a type 2 cytokine that is produced at high levels in the mucosa of UC patients. MDV3100 datasheet Hence, TGF-β promotes the normal resolution of intestinal inflammation at least in part, through limiting the production of type 2 cytokines from colonic Mϕs. CD68

(macrosialin) encodes a type 1 transmembrane protein in mononuclear phagocyte endosomes and its promoter drives Mϕ-specific transgene expression in mice 27, 37. We demonstrate that the CD68 promoter drives transgene expression in colonic F4/80+ and F4/80+ CD11c+ populations, but is only marginally expressed in CD11c+ (specific for dendritic cells) or Gr-1+ cell populations (specific for neutrophils/granulocytes) (Fig. selleck screening library 2) (data not shown). This is distinct from all other myeloid-specific promoters such as human CD11b, c-fms, and lysozyme that confer dendritic cell- and neutrophil-specific expression 38–40. Neutrophils promote oxidative tissue injury during DSS-induced colitis 41 and

TGF-β is known to directly modulate neutrophil function in vivo 42, which makes the lack of transgene expression in granulocytes an important issue in this model system. Our data are consistent with prior evidence that the human CD68 promoter is primarily active in mature tissue-resident Mϕ populations 43, 44. Prior to colitis induction, CD68

TGF-βDNRII mice do not have signs of overt inflammation or tissue injury. On the contrary, mice that lack STAT-3 responsiveness in Mϕs and neutrophils develop spontaneous colitis by 20 wk of age 45. As STAT-3 is an important transcription factor for IL-10 responses 46, this may suggest distinct roles for IL-10 and TGF-β in the regulation of gastrointestinal inflammation. Exacerbated intestinal immunopathology following the cessation of DSS administration in CD68 TGF-βDNRII mice was associated with an extended period of granulocyte infiltration, G-CSF production, chemokine release, and myeloperoxidase (MPO) production (data not shown). This is consistent Demeclocycline with prior evidence in this model that excess accumulation of activated Mϕs, neutrophils, eosinophils causes irreparable mucosal damage and lethality 47, 48. Insufficient IL-10 production may partially explain the increased inflammation in CD68TGF-βDNRII mice, as IL-10-mediated suppression of colitis can be TGF-β dependent 49 and TGF-β induces Mϕs to produce IL-10 34. Furthermore, Mϕs from CD68TGF-βDNRII mice produced significantly less IL-10 following TGF-β stimulation in vitro (Fig. 1E) and in vivo (Fig. 5B and C). This link between TGF-β responsiveness in Mϕs and IL-10 production is consistent with evidence that TGF-β suppresses intestinal inflammation via regulatory Mϕs that produce IL-10 50.

The data were analysed https://www.selleckchem.com/products/forskolin.html using the two-sided Student’s t-test. Differences were considered to be statistically

significant at P < 0.05. To evaluate whether coadministration of APS and hepatitis B vaccine can enhance humoral and cellular immune responses, mice were intramuscularly immunized with rHBsAg alone, rHBsAg + APS or rHBsAg + alum. On day 7 after the second immunization, serum was collected and the total IgG antibody against rHBsAg was analysed by quantitative ELISA. The level of antibody was significantly increased in mice immunized with rHBsAg + APS compared with mice immunized with rHBsAg alone or rHBsAg + alum (Fig. 1a). For detection of cellular immune response, T lymphocytes were isolated from the immunized mice on day 7 after the second immunization and stimulated with HBsAg as the specific antigen, concanavalin A as a positive control, bovine serum albumin as a nonspecific control and medium as negative

control. The proliferative response was significantly enhanced in the group immunized with HBsAg + APS buy Kinase Inhibitor Library compared with other groups (Fig. 1b). T helper (Th) cytokine expression was also detected in CD4+ T cells by fluorescence-activated cell sorting (FACS). As shown in Fig. 2, mice immunized with HBsAg + APS induced the highest levels of IL-2, IL-4 and IFN-γ in CD4+ T cells compared with other

groups. As expected, alum increased IL-4 production, but this increase was less than the either APS group. These results demonstrated that APS can enhance both humoral and cellular immune responses. The adjuvant effect of APS on antigen-specific cytotoxic response was also detected after the second immunization. An in vivo CTL assay was performed on day 7 after the second immunization. As shown in (Fig. 3a), the percentages of antigen-specific lysis of the target cells in mice immunized with HBsAg, HBsAg + APS or alum and APS alone were 6.8, 40%, 4.3% and 6.2%, respectively. HBsAg + APS induced the highest CTL activity among all the groups. The results suggested that APS as adjuvant could significantly augment antigen-specific CTL activities in immunized mice. It is well known that T cytotoxic lymphocytes can directly clear HBV via effect molecules such as PFP, Gra B, Fas L and Fas, or by indirectly interfering with the replication of the virus in infected cells with IFN-γ (Chisari, 1997, 2000). The mRNA levels of these genes were analysed by semiquantitative reverse transcriptase PCR (RT-PCR) on day 7 after the second immunization. The production of IFN-γ in CD8+ T cells was detected by FACS. As depicted in (Fig.

In addition, the expression of IL-6 and CXCL1 in mouse embryonic fibroblast (MEF) cells was significantly increased by the ES protein treatment, but we did not detect these effects in the TRIF−/− CH5424802 ic50 MEF cells. These elevations of IL-6 and CXCL1 expression were also not diminished by RNase treatment. In conclusion, the ES proteins of helminthic parasite larva may elicit TRIF dependent pro-inflammatory cytokines, and this is not double-stranded RNA. Roundworms have been found to be able to infect most mammals, and also exhibit host specificity. Most of the roundworms generally evidence a visceral larva migration period during their life cycle, which is essential for their development into adult worms.

During the larva migration period, most larvae can move to the lung through disrupted ERK inhibitor alveoli, migrate via the bronchi, trachea, pharynx and are then swallowed (1).

When the larvae break through the lung tissue and into the alveoli, damage to the bronchial epithelial cells may occur. A pronounced tissue reaction in the lung may also occur around the larvae, with an attendant infiltration of immune cells (1,2). Many case reports have noted that roundworm larva can cause asthma, pneumonia and airway inflammation (2–4). Anisakis simplex has also been identified as an allergen which elicits allergic inflammation in experimental and clinical patients (5,6). Humans become infected with A. simplex (anisakidosis) via the consumption of marine fish or cephalodods contaminated by third stage larvae. After oral ingestion, the larvae penetrate into the gastric or intestinal wall, thereby inducing

severe pain and profound immune responses in humans (6–8). Although A. simplex often exploits the oral infection MycoClean Mycoplasma Removal Kit route, it can occasionally cause airborne asthma without further problems after the host consumes fish; Anisakis has also been implicated in some allergen-related issues (9–14). Interleukin-17A and IL-17F are members of the IL-17 family that perform critical roles in allergic inflammation. Recent studies have reported that IL-17A and IL-17F production from a distinct Th lymphocyte subset, Th17, was specifically induced by IL-23 that was generated by dendritic cells and macrophages in response to microbial stimuli. The IL-23-IL-17 axis may therefore constitute a link between infections and allergic diseases (15–17). Recently, IL-17A, IL-17F and IL-23 have been shown to induce the release of chemokines CXCL1 (Gro-alpha), CXCL8 (IL-8) and CCL4 (MIP-1beta) from eosinophils (17). Certain helminth parasite-derived molecules have been reported that could activate pro-inflammatory cytokines and immune response via several types of toll-like receptors (TLR). Most of these have focused principally on the glycans of schistosomes and TLR2, as well as the wolbachial endosymbiont of the filariae and TLR2 and TLR4 (18–20).

[26-29] We and others have shown that high serum Fet-A RR are found in patients with pre-dialysis and dialysis-dependant CKD.[20, 30] We have also shown that serum Fet-A RR are independently associated with vascular stiffness in patients with pre-dialysis CKD and are strongly correlated with systemic inflammatory status.[30] In this study we set out to compare Selleck LEE011 serum Fet-A concentrations and Fet-A RR in patients across the spectrum of CKD, including a subset of patients with calcific uraemic

arteriolopathy (CUA), and in those with chronic inflammatory disease but normal renal function. One hundred and seven participants were enrolled in an observational study of Fetuin Levels in Systemic disease and Kidney Impairment (FLEKSI). Sixty-four patients were attending clinics at Box Hill Hospital (BHH) from October 2011 until March

2012. These included 11 patients with pre-dialysis Stages 3 & 4 CKD (‘CKD’ group), 15 prevalent haemodialysis patients (‘HD’ group) and 18 patients undergoing peritoneal dialysis (‘PD’ group). A further group of 13 patients with active chronic inflammatory Talazoparib disease but normal renal function (‘CID’ group), were recruited from the rheumatology outpatients department at BHH and included individuals with: Rheumatoid arthritis (n = 5), Systemic lupus erythematosus (n = 3), Polyarteritis nodosum (n = 2), Giant cell arteritis (n = 1), Wegener’s

granulomatosis without renal involvement (n = 1), Takayasu’s arteritis (n = 1) (this case has been previously described.[31] Twenty-six prevalent HD patients were recruited from a study at the Royal Melbourne Hospital. We specifically sought out a cohort of patients with CUA (n = 6), all of whom were on HD. These patients had clinically diagnosed CUA, biopsy-proven triclocarban disease or were currently being treated/managed for CUA. Apart from this group, all dialysis patients were stable without evidence of ongoing intercurrent illness and who were achieving small molecule clearance targets. All HD patients were receiving conventional HD thrice weekly (on average 4 h per session) with a dialysis solution containing 1.3 mmol/L calcium, and dialysing with Polysolfone® membranes (Fresenius Medical Care AG & Co, Bad Homburg, Germany). Dialysate was regularly monitored for impurities (<0.1 CFU/mL, <0.03 EU/mL endotoxins). Exclusion criteria included known pregnancy, age less than 16 years or greater than 90 years. A detailed drug history was recorded on all patients, making particular note of over the counter preparations including cholecalciferol or activated vitamin D analogues. Twenty-four healthy adult subjects were enrolled from staff and volunteers at BHH.

At 8 weeks after surgery, the CD-augmented tissues contained layered SMA-positive cells, urothelium uroplakin PD-0332991 nmr III -positive urothelium, and S100 fibers, similar to normal bladder tissue. The SIS-augmented bladders showed similar results. At 8 weeks after augmentation, the bladder volume of CD-augmented bladders was larger than that at 4 weeks, while the SIS-augmented bladders were the same as those at 4 weeks. The bladder volume of the non-augmented group did not increase. The bladder compliance of the

CD-augmented bladders at 8 weeks was significantly higher than at earlier times. The bladder compliance of neither the non-augmented nor the SIS-augmented groups increased during the study period. Conclusion: Acellular bovine pericardium-derived material could be a suitable biomaterial for bladder augmentations “
“Many theories attempt to explain the complex etiology of overactive bladder syndrome (OAB), but the exact mechanisms of the pathophysiology Endocrinology antagonist have yet to be fully

understood. Recent findings have suggested that hypercholesterolemia is related with detrusor overactivity (DO), which, in turn, is usually associated with OAB. The present report examines published studies that have associated hypercholesterolemia with DO to determine the grounds on which such studies were based. According to our analysis, OAB and DO are closely related with hypercholesterolemia. Furthermore, DO and OAB may be affected not just by a single factor like hypercholesterolemia, but rather by all components of metabolic syndrome. Several mechanisms, including

autonomic overactivity, artherosclerosis, ischemic change, alteration of nitric oxide synthase (NOS)/NO system and increased Rho-kinase activity may have a role in the relationship between OAB and hypercholesterolemia. Further studies are warranted, however, to evaluate more about the pathophysiology of OAB. Overactive bladder syndrome (OAB) is characterized by an “urgency, with or without urge incontinence, usually with frequency and nocturia”, and detrusor overactivity (DO) is a urodynamic observation characterized by involuntary detrusor contractions during the filling phase and may Phospholipase D1 be spontaneous or provoked according to the International Continence Society.1 The diagnosis of OAB does not require urodynamic confirmation of DO, although it often is stated that the patient-reported sensation of urinary urgency is the result of a concomitant involuntary detrusor contraction.2 Hence, DO is often, but not invariably, associated with OAB.3 The pathophysiology of OAB is difficult to explain with simply one etiology. Neurologic dysfunction, as well as obstruction-related, congenital, behavioral, age-related, myogenic, ischemic, inflammatory, and many other factors are considered to be causes of OAB.4–6 Likewise, the pathophysiological basis of DO remains incompletely understood.

Immune cells in the pre-menopausal FRT exist in an environment that is continuously exposed to changing levels of sex hormones. As previously described, several

antimicrobials in CVL or CVM vary with stage of the menstrual cycle. However, the contribution of individual cell types within the FRT toward total antimicrobial production remains relatively understudied with the bulk of research being performed on FRT epithelial cells. As seen in Table IV, we and others have isolated purified uterine epithelial and stromal cells from hysterectomy patients. Under estradiol stimulation, this website uterine epithelial cells upregulate the production of SLPI, HBD2 and Elafin.72,77 However, the antimicrobial profile of human uterine stromal cells and their response to hormonal stimulation is unknown. In the lower FRT, we observed a very different

response, with vaginal epithelial cells decreasing the secretion of HBD2 and Elafin after 48 hrs of estradiol treatment (Patel et al. unpublished observation). Inhibition progressively increases from 10−8 to 10−10m. In our system, uterine epithelial cells were strong constitutive producers of MIP3α38– an antimicrobial absent from vaginal epithelial cell cultures (Patel et al. unpublished observation). Thus, the vaginal compartment possesses markedly dissimilar responses compared to the uterus – possibly the result of their different embryonic origins, or the differential expression of find more co-activator molecules in epithelial cells. Estradiol can also modulate innate immune responses to pathogenic stimuli. For example, estradiol inhibits the LPS-mediated upregulation of IL-6 in uterine epithelial Clomifene cells.72,77 Whether estradiol influences antimicrobial production in a similar manner remains unknown. The effects of progesterone upon epithelial cells are less well studied (Table IV). We found that progesterone has no effect on HBD2 and Elafin production by fresh primary human vaginal epithelial

cells (Patel et al. unpublished observation). Endometrial explants from the proliferative or secretory phase show a differential response to progesterone. Proliferative phase tissue decreased the mRNA production of HBD1 and HBD2 but increased SLPI in response to progesterone (10−6 m).78 In contrast, no progesterone effect was observed with secretory tissue. As neither estradiol nor progesterone exists alone in the FRT, further studies are needed to investigate the combined effects of these hormones to more accurately represent the in vivo environment. Studies on immune cells recovered from the FRT are limited. It is essential to understand the effects of hormonal stimulation on these cells, as they are a rich source of antimicrobials. For example, neutrophils contain high concentrations of alpha defensins in their granules and are present in greater numbers in the upper FRT during ovulation.