Interleukin-17, produced by lymphocytes, promotes tumor growth and angiogenesis in a mouse model of breast cancer.

Previous studies have suggested that interleukin-17 (IL-17), an inflammatory cytokine expressed predominantly by Th17 cells, is highly expressed in tumor tissue and may help tumors to evade immune surveillance. In this study, the significance of IL-17 expression in the tumors of murine models of breast cancer was explored. BALB/c mice were injected with MA782/5S28102 or 4T1 breast cancer cell lines to establish breast tumors. The expression of IL-17 in tumor tissue was detected by western blotting 1 and 4 weeks later, which revealed that it increased with tumor progression (P<0.05). Additionally, tumor cells and tumor-infiltrating lymphocytes were isolated from tumor tissues and cultured for 5 days with stimulation by phorbol-12-myristate-13-acetate (PMA), anti­CD3 antibody and anti-CD28 antibody. Culture media from stimulated tumor cells or tumor-infiltrating lymphocytes were harvested and their concentrations of IL-17 were tested by ELISA. Tumor cells secreted low levels of IL-17 into the media; however, lymphocytes from tumor tissues secreted high levels of IL-17, with 4T1 tumors secreting higher levels of IL-17 than MA782 tumors (P<0.05). To evaluate the effect of IL-17 on the proliferation of tumor cells, 4T1 cells were cultured in the presence or absence of recombinant IL-17 and cell numbers were counted on day 5 of culturing. Ectopic IL-17 did not promote the proliferation of tumor cells in vitro. To further understand the effect of IL-17 expression within tumors, 4T1 tumor-bearing mice were injected with recombinant IL-17 or saline via the tail vein. Tumor size was measured up to 21 days following the initial infusion of IL-17. IL-17 infusion resulted in an increased tumor volume and microvascular density (as measured by the immunohistochemical detection of CD34 expression in microvessels; P<0.05). Therefore, IL-17 expression within tumor tissues appears to originate from tumor-infiltrating lymphocytes and is likely to promote tumor growth by enhancing angiogenesis.

Association between mutations of the luteinizing hormone ß subunit and female infertility.

To explore the association between mutations of Trp8Arg and Ile15Thr in the luteinizing hormone (LH) gene and female infertility, primary female infertility patients (n=60) and normal healthy women (n=60) were screened for mutations Trp8Arg and Ile15Thr in the LH-ß subunit gene by polymerase chain reaction-restriction fragment length polymorphism, and associations were examined between the mutations and female infertility. The results showed that there were significant differences in the allele and genotype frequencies of Trp8Arg and Ile15Thr between the two groups (P<0.05). A significant difference was noted in the LH level among women with different genotypes (P<0.05), and the LH level was highest in women who were homozygous for both mutations. However, there were no significant differences in FSH level and FSH/LH ratio among subjects with different genotypes (P>0.05). In conclusion, polymorphisms of Trp8Arg and Ile15Thr in the LH-ß subunit gene occur in infertile women. The polymorphisms correlate with female infertility and may be a risk factor in the pathogenesis of female infertility.

Polymorphisms in estrogen receptor-α are associated with idiopathic female infertility.

To investigate the relationship between polymorphisms in the estrogen receptor-α (ERα) gene and unexplained female infertility, restriction fragment length polymorphism (RFLP) analysis of ERα was employed in 150 females with idiopathic infertility (study group) and 150 healthy, age-matched females of proven fertility (control group). The results showed that the ERα allele frequencies differed significantly between the study and control groups (P=0.001). The allele identified by PvuII (P) restriction was detected more frequently in the study group (49.0% of individuals) compared to the control group (31.0%; P=0.001), while the allele identified by XbaI (X) restriction was detected less frequently in the study group (19.7%) compared to the control group (35.7%, P=0.001). A similar phenomenon was observed for the distribution of the TA alleles. The TA13 allele was more common in the study group (24.7 vs. 6.7% in controls; P=0.001), while the TA15 allele was less common in the study group (15.3 vs. 27.3% in controls; P=0.034). To conclude, polymorphisms in the ERα gene are associated with idiopathic female infertility. In particular, the P and TA13 alleles may represent significant risk factors, while the X and TA15 alleles may be protective factors.

Th1 immunity is not required for the effect of lipopolysaccharide exposure on modifying asthmatic responses of mice before sensitization.

BACKGROUND: Disequilibrium of Th1/Th2 is known as an important cause of allergic asthma with a biased Th2 type response. It has been shown that lipopolysaccharide (LPS) administration during post-sensitization modified the inflammation of asthma via upregulating the Th1 response that decrease the Th2 immunity. We would like to know if, during pre-sensitization, the elevated Th1 response is necessary for LPS exposure to modify the asthmatic response. METHODS: During pre- or post-sensitization, 40 microg LPS were intraperitoneal injected (i.p.) to asthmatic mice sensitized and challenged by Dermatophagoides farinae (D. farinea). Inflammation was assessed by examining bronchoalveolar lavage fluid (BALF) for the number and identity of cells and by cytokine titers measured by ELISA. Semi-quantified RT-PCR was used to evaluate the level of Toll-like receptor 4 (TLR4) mRNA in dendritic cells (DCs) from bone marrow (BMDCs). RESULTS: These investigations demonstrated that LPS exposure during pre-sensitization inhibited the Th2 cytokine and inflammatory infiltration, the same as with LPS exposure during post-sensitization in allergic asthma mice. Contrary to post-sensitization LPS exposure, the Th1 cytokines were not upregulated by pre-sensitization with LPS. Finally, the study failed to show any significant difference between TLR4 mRNA expressed in BMDCs with the two times of LPS exposure. CONCLUSIONS: Our data suggest that elevated Th1 immunity is not required for the modification of the Th2 response induced by LPS exposure during pre-sensitization in asthmatic mice and that pre-sensitization differs from post-sensitization. Immune modulation with treatment is independent of TLR4 expression in BMDCs. This study implicates a potential way to protect from allergic disease and an inflammatory response.