Cellular and molecular mechanisms of intestinal fibrosis

Table 3 Predominant pro-fibrotic cytokines

Cytokines	Role in fibrosis	Ref.
IL-1/IL-33	Activate myofibroblasts	[144,146]
	Stimulate TGF expression	[145]
	Regulate chemokines, cytokines and MMPs secretion	[144]
IL-4/IL-13	Activate myofibroblasts	[147]
	Increase deposition of collagen I, III and IV	[148]
	Induce production of latent TGF-β and activate TGF-β	[152,153]
	Promote fibrocyte differentiation	[154]
IL-6	Stimulates proliferation of fibroblasts	[157]
	Modulates TGF-β and TGF-βRII	[156]
	Its neutralization improves fibrosis	[155]
IL-21/IL-22	Stimulate the expression of IL-4, IL-13 and IL-17	[159]
	Increase secretion of ECM degrading enzymes	[160]
	Maintain the integrity of the epithelial barrier	[161]
	Inhibit deposition of collagen	[163]
IL-17/IL-23	Maintain chronic inflammation in the gut	[143]
	Induce activation and proliferation of myofibroblasts	[165]
	Stimulate deposition of collagen	[164]
TNFα	Stimulates intestinal myofibroblast proliferation	[170]
	Stimulates deposition of collagen	[171]
	Inhibits collagen degradation through TIMP-1 induction	[172,173]

TNF: Tumor necrosis factor; ECM: Extracellular matrix; IL: Interleukin; TGF-β: Transforming growth factor-β; TIMPs: Tissue inhibitors of metalloproteinases; MMPs: Matrix metalloproteinases.