Mucus mediated protection against acute colitis in adiponectin deficient mice

Abstract

BackgroundAcute ulcerative colitis is an inflammation-driven condition of the bowel. It hampers the general homeostasis of gut, resulting in decreased mucus production and epithelial cell renewal. Adiponectin (APN), an adipocytokine, is secreted by the adipose tissue and has been debated both as a pro-inflammatory or anti-inflammatory protein depending on the disease condition and microenvironment. The present study delineates the role of APN depletion in mucus modulation in a model of acute colitis.MethodsAPNKO and C57BL/6 (WT) male mice were given 2% DSS ad libidum for 5 days in drinking water, followed by normal drinking water for the next 5 days. Hematoxyline-eosin and Alcian Blue staining was used to observe the general colonic morphology and goblet cell quantification respectively. Protein expression levels were quantified by Western blot for MATH1, Hes1, MUC2 and MUC4. ELISA was used to study the levels of TNF-α, IL-6 and IL-1β.ResultsAPNKO mice showed significantly higher goblet to epithelial cell ratios, lower pro-inflammatory cytokines and higher MUC2 levels as compared to the WT mice. The protein expression levels for the mucin MUC2 supported the histopathological findings. An increase in colon tissue-secreted levels of pro-inflammatory with a reduction in anti-inflammatory cytokines in presence of APN support the pro-inflammatory role of APN during acute inflammation.ConclusionAbsence of APN is protective against DSS-induced acute colonic inflammation by means of reducing colon tissue-secreted pro-inflammatory cytokines, modulating goblet and epithelial cell expressions, and increasing the levels of secretory mucin MUC2.

Antibiotic‐mediated bacteriome depletion in ApcMin/+ mice is associated with reduction in mucus‐producing goblet cells and increased colorectal cancer progression

“…Depletion of bacterial communities reduced goblet counts that could be attributed to either regulation of goblet cell apoptosis or goblet cell development or both. Goblet cells are integral to the maintenance of the mucus layer, which in turn, regulates the composition of the gut microflora (findings from previous studies [64]). As mucus layer offer protection against inflammation and tumor progression [44], factors that disrupts this protection cycle will lead to gut inflammation and carcinogenesis.…”

Adiponectin confers protection from acute colitis and restricts a B cell immune response

“…Likewise, in another independent study, WT mice treated with DSS and an APN adenovirus were protected (50). In marked contrast, the work of Fayad et al (51,52) reported that DSS treatment and APN absence was protective against colitis, and a reduced inflammatory response was observed. These differences could be explained by variations in methods, the source of KO mice, the form of recombinant APN, and the pathogen status of the animal facilities.…”

Role of Obesity, Mesenteric Adipose Tissue, and Adipokines in Inflammatory Bowel Diseases

“…The hypothesis on the protective role of adiponectin in colitis, acting through AdipoR1, is supported by the evidence from Sideri et al [127], who showed that intracolonic AdipoR1 knock down worsened TNBS-induced colitis in mice. In contrast, some studies [211,212] report that APN absence protects against DSS induced colitis. In another study, APN deficiency did not significantly modulate the inflammation in the IL-10 KO model of spontaneous chronic colitis [213].…”