Goat anti Rat IL1A polyclonal antibody [Biotin]

Inflammatory bowel disease (IBD) is a multifactorial disease involving defective immune responses against invasive microbiota. Genes associated with innate immune responses to microbes have been highlighted in the pathogenesis of IBD. To determine the role of Rab32 in the pathogenesis of IBD, we administered dextran sodium sulfate (DSS) to CD11c(+) cell-specific Rab32 knockout (CD11c-Cre(+)Rab32(f/f)) mice to induce colitis. Rab32 deficiency in CD11c(+) cells resulted in more severe disease progression and increased mortality. Histopathological analysis showed extensive damage to the colon mucosa in DSS-treated CD11c-Cre(+)Rab32(f/f) mice, including more severe damage to the epithelial layer and crypts, as well as more inflammatory cell infiltration. The pro-inflammatory cytokines IL1A, IL1B, IL6, and CSF3 and chemokines CXCL1 and CXCL2 were significantly increased, and the frequency of CD11b(+)Ly6G(+) neutrophils was higher in CD11c-Cre(+)Rab32(f/f) colitis mice. Furthermore, CD11c(+) cells deficient for Rab32 exhibited a significant increase in bacterial translocation in inflamed colon tissue. The present data demonstrate that Rab32 knockout in CD11c(+) cells aggravates the development of DSS-induced colitis and suggest that the Rab32-related antimicrobial pathway is involved in the pathogenesis of IBD.

The homeostasis of the epidermis depends on keratinocyte differentiation and cornification, a mode of programmed cell death that does not elicit inflammation. Here, we report that cornification is associated with the expression of specific genes that control multiple steps of pyroptosis, another form of cell death that involves the processing and release of interleukin-1 family (IL1F) cytokines. Expression levels of pro-inflammatory IL1A and IL1B and of the pyroptotic pore-forming gasdermin (GSDM) D were downregulated during terminal differentiation of human keratinocytes in vitro. By contrast, negative regulators of IL-1 processing, including NLR family pyrin domain containing 10 (NLRP10) and pyrin domain-containing 1 (PYDC1), the anti-inflammatory IL1F members IL-37 (IL1F7) and IL-38 (IL1F10), and GSDMA, were strongly induced in differentiated keratinocytes. In human tissues, these keratinocyte differentiation-associated genes are expressed in the skin at higher levels than in any other organ, and mammalian species, that have lost the epidermal cornification program during evolution, i.e. whales and dolphins, lack homologs of these genes. Together, our results suggest that human epidermal cornification is accompanied by a tight control of pyroptosis and warrant further studies of potential defects in the balance between cornification and pyroptosis in skin pathologies.