S1f). tristetraprolin expression operates through CREB and NF-B transcription factors, which in turn, regulates the stability of chemokines. Together, our findings suggest that ANGPTL4 protects against acute colonic inflammation and that its absence exacerbates the severity of inflammation. Our findings emphasize the importance of ANGPTL4 as a novel target for therapy in regulating and attenuating inflammation. An aggravated inflammatory response is usually a common feature of many gastrointestinal disorders, such as inflammatory bowel diseases, enteritis, and colitis. Many of these conditions are caused by changes in dietary fat intake, the ingestion of bacteria-contaminated food and water, and certain chemicals. These insults trigger an inflammatory response by inducing the recruitment of macrophages to the site of inflammation to combat pathogens, neutralize harmful immunogens and promote tissue repair1. However, a protracted inflammatory response can cause tissue damage and lead to hypercytokinaemia, which is a potentially fatal immune reaction. Immune cell infiltration into the site of damage is usually highly regulated by chemotactic factors, such as macrophage inflammatory protein 1 and chemokine (C-C motif) ligand 2 (CCL2)2,3. As the initial cellular barrier that encounters lumenal insults, intestinal and colonic epithelia play important roles in the early recruitment of inflammatory cells to the mucosa. Epithelial cells are a major source of chemoattractants, and epithelial chemokine production has been proposed as a key target of future therapies for gastrointestinal disorders4. However, much remains to be comprehended about the mechanisms that regulate the levels of these chemokines in the gastrointestinal and colonic tracts. Angiopoietin-like 4 (ANGPTL4) is usually a matricellular protein that has been implicated in many inflammation-associated diseases5. Native full-length ANGPTL4 (fANGPTL4) is usually proteolytically cleaved into two functionally distinct isoforms: the IQ 3 N-terminal domain name (nANGPTL4) inhibits lipoprotein lipase (LPL) and directly regulates energy homeostasis, while the C-terminal domain name (cANGPTL4) has been implicated in various processes such as cancer metastasis, skin wound and pulmonary inflammation6,7,8. Diabetic wounds show low endogenous cANGPTL4 levels and have been associated with an elevated F4/80+ macrophage population at the wound site. The infiltration of F4/80+ macrophages was reduced upon treatment of diabetic wounds with recombinant cANGPTL4 when compared with saline9. ANGPTL4 can also protect against the severe pro-inflammatory effects of saturated fat by inhibiting fatty acid uptake by mesenteric lymph node macrophages10. Similarly, ANGPTL4 confers protective effects against the development of atherosclerosis11, which has been associated with atherogenesis and macrophage polarization12. ANGPTL4 has also been identified as an angiogenic mediator in arthritis13. ANGPTL4 has been observed to exacerbate influenza-associated inflammation through IQ 3 IL-6CStat3 signaling in the lung14. Furthermore, serum ANGPTL4 was associated with the C-reactive protein level in type II diabetic patients, suggesting that ANGPTL4 may be involved in the progression of inflammation during metabolic IQ 3 syndrome15. Thus, ANGPTL4 may exert both anti- and pro-inflammatory effects in a context-dependent manner. Despite numerous reports of the role of ANGPTL4 in inflammation, the mechanisms whereby ANGPTL4 modulates inflammation in various diseases remain largely unclear. Herein, we describe an anti-inflammatory role for colonic ANGPTL4 in dextran sulfate sodium salt (DSS)-induced colitis and dietary stearic acid (SA) intake and Rabbit Polyclonal to Caspase 7 (Cleaved-Asp198) We showed that this microbiota was comparable between ANGPTL4+/+ and ANGPTL4?/? mice at steady says, but with perturbation such as DSS treatment some differences in microbiota community become accentuated. Bone marrow transplantation and microarray analysis confirmed the intrinsic role of colonic ANGPTL4 in regulating leukocyte infiltration during DSS-induced inflammation, and thus the colonic inflammatory landscape. The underlying mechanism involves the regulation of tristetraprolin (TTP or ZFP36), an mRNA-binding protein that is.