Sexual dimorphism in innate immunity

Moxley, George; Posthuma, Daniëlle; Carlson, Patricia; Estrada, Eloise; Han, Jinfeng; Benson, Linda L.; Neale, Michael C.

doi:10.1002/1529-0131(200201)46:1<250::aid-art10064>3.0.co;2-t

Cited by 111 publications

(62 citation statements)

References 43 publications

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“…There was a great individual variability in mRNA expression levels of the different cytokines in dogs with FRD, IBD and even in control dogs. Differences in age, growth, sex and (or) nutritional status probably also accounted for the variability in cytokine mRNA profiles, in agreement with studies in humans (Moxley et al, 2002;Grimble, 2003;Huang et al, 2005). However, there were significant gender influences on INF-γ mRNA levels of FRD dogs and on IL-13 mRNA levels in IBD dogs in duodenal samples.…”

Section: Discussionsupporting

confidence: 84%

Cytokine mRNA abundance in intestinal biopsies from dogs with chronic diarrhea

Sauter¹,

Allenspach²,

Blum³

2007

Vet. Med. - Czech

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ABSTRACT:The differentiation between inflammatory bowel disease (IBD) and food responsive diarrhea (FRD) is difficult and no objective markers are available. We postulated that patterns of selected key cytokines would help to objectively differentiate between the two subcategories of chronic enteropathies in dogs. We studied mRNA patterns of selected cytokines in dogs with chronic enteropathies. Ten dogs with FRD (= group FRDbef ) and seven dogs with IBD (= group IBDbef ) were presented for endoscopy at the Small Animal Clinic, University of Bern. A control endoscopy was performed in both groups after treatment with an elimination diet for four weeks (FRDaft) or with an elimination diet combined with prednisolone for 10 weeks (IBDaft). Intestinal control samples of gastrointestinally healthy dogs from an independent study were additionally available. Dogs were clinically examined and scored using the canine IBD activity index (CIBDAI). mRNA abundance of interleukin (IL)-5, -10, -12p40, and -13, tumor necrosis factor (TNF)-α, transforming growth factor (TGF)-β1, and interferon (IFN)-γ were analyzed in intestinal samples by reverse transcription and real time polymerase chain reaction. Median CIBDAI decreased in FRDaft (P < 0.01) and IBDaft (P = 0.07) during treatment. In duodenum, IL-12p40 mRNA levels tended to be lower in FRDbef than in IBDbef (P = 0.07). The abundance of TNF-α mRNA was higher in IBDbef than in control dogs (P < 0.05). IL-5 mRNA levels decreased in FRD dogs during treatment (P = 0.06), and IL-10 mRNA levels decreased in IBD dogs (P < 0.05). In colon, IL-5 and IL-12p40 mRNA levels were lower in FRDbef than in IBDbef (P < 0.05) and control dogs (P < 0.01). IL-13 mRNA abundance was lower in FRDbef than in control dogs (P < 0.05) and IFN-γ mRNA abundance was lower in FRD and IBD dogs than in control dogs (P < 0.01). Feeding the elimination diet additionally reduced IFN-γ mRNA levels (P < 0.01), but increased TNF-α mRNA levels (P < 0.05) in FRD dogs. In conclusion, mRNA levels of the selected cytokines before treatment did not show clear differences between FRD and IBD dogs.

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Section: Discussionsupporting

confidence: 84%

Cytokine mRNA abundance in intestinal biopsies from dogs with chronic diarrhea

Sauter¹,

Allenspach²,

Blum³

2007

Vet. Med. - Czech

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“…Previous reports have investigated the sexual dimorphism of protein-coding gene expression and the effect of sex hormones in the regulation of protein-coding genes with focus on immune response genes in both human and mouse immune cells [50-52]. In this study, we are the first to show sex differences in the expression of small, non-protein-coding RNAs (miRNAs) in lupus-prone NZB/W F1 mice.…”

Section: Discussionmentioning

confidence: 86%

Sex differences in the expression of lupus-associated miRNAs in splenocytes from lupus-prone NZB/WF1 mice

et al. 2013

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BackgroundA majority of autoimmune diseases, including systemic lupus erythematosus (SLE), occur predominantly in females. Recent studies have identified specific dysregulated microRNAs (miRNAs) in both human and murine lupus, implying an important contribution of these miRNAs to lupus pathogenesis. However, to date, there is no study that examined sex differences in miRNA expression in immune cells as a plausible basis for sex differences in autoimmune disease. This study addresses this aspect in NZB/WF1 mice, a classical murine lupus model with marked female bias, and further investigates estrogen regulation of lupus-associated miRNAs.MethodsThe Taqman miRNA assay system was used to quantify the miRNA expression in splenocytes from male and female NZB/WF1 mice at 17–18, 23, and 30 weeks (wks) of age. To evaluate potential estrogen's effect on lupus-associated miRNAs, 6-wk-old NZB/WF1 male mice were orchidectomized and surgically implanted with empty (placebo) or estrogen implants for 4 and 26 wks, respectively. To assess the lupus status in the NZB/WF1 mice, serum anti-dsDNA autoantibody levels, proteinuria, and renal histological changes were determined.ResultsThe sex differences in the expression of lupus-associated miRNAs, including the miR-182-96-183 cluster, miR-155, miR-31, miR-148a, miR-127, and miR-379, were markedly evident after the onset of lupus, especially at 30 wks of age when female NZB/WF1 mice manifested moderate to severe lupus when compared to their male counterparts. Our limited data also suggested that estrogen treatment increased the expression of aforementioned lupus-associated miRNAs, with the exception of miR-155, in orchidectomized male NZB/WF1 mice to a similar level in age-matched intact female NZB/WF1 mice. It is noteworthy that orchiectomy, itself, did not affect the expression of lupus-associated miRNAs.ConclusionTo our knowledge, this is the first study that demonstrated sex differences in the expression of lupus-associated miRNAs in splenocytes, especially in the context of autoimmunity. The increased expression of lupus-associated miRNA in female NZB/WF1 mice and conceivably in estrogen-treated orchidectomized male NZB/WF1 mice was associated with lupus manifestation. The notable increase of lupus-associated miRNAs in diseased, female NZB/WF1 mice may be a result of both lupus manifestation and the female gender.

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“…Moxley et al found that in comparison to men, healthy female subjects have significantly lower tumor necrosis factor-␣ production after lipopolysaccharide stimulation. This difference seems to be explained not only by hormonal disparity, but also by the presence of a microsatellite haplotype into the tumor necrosis factor locus (49). The fact that IRAK1 is located on the X chromosome implies that a higher percentage of men will be carrying the variant genotype than women, because female genotypes are distributed into WT, heterozygous, and homozygous.…”

Section: Discussionmentioning

confidence: 99%