Gut inflammation: current update on pathophysiology, molecular mechanism and pharmacological treatment modalities - PubMed (original) (raw)
Review
Gut inflammation: current update on pathophysiology, molecular mechanism and pharmacological treatment modalities
Klára Gyires et al. Curr Pharm Des. 2014.
Abstract
Inflammatory bowel disease (IBD) is a chronic and relapsing inflammatory condition of the gastrointestinal tract. The two main forms of IBD are Crohn's disease and ulcerative colitis. According to the recent concept the disease is caused by a combination of factors, including genetics, immune dysregulation, barrier dysfunction and the change in microbial flora. Environmental factors, such as changes in diet, antibiotic use, smoking or improved domestic hygiene (e.g. eradication of intestinal helminths) probably contribute to the development and increased prevalence of IBD. Dysregulation of mucosal immunity in IBD causes an overproduction of inflammatory cytokines which resulted in uncontrolled intestinal inflammation. Based on extensive research over the last decade, besides the conventional therapy, there are several novel pathways and specific targets, on which focus new therapeutics. New therapeutics aim 1./ to correct genetic susceptibility by stimulating NOD2 expression, TLR3 signaling or inhibition of TLR4 pathway, 2./ to restore the immune dysregulation by inhibition of pro-inflammatory cytokines (TNF-α, IL-6, IL-13, IL-17, IL-18, IL-21), Th1 polarisation (IL-2, IL-12, IL-23, IFN-γ ), T-cell activation, leukocyte adhesion, as well as by immunostimulation (GM-CSF, G-CSF) and anti-inflammatory cytokines (IL-10, IL-11, IFN-β-1a), 3./ to restore mucosal barrier function and stimulate mucosal healing by different growth factors, such as GH, EGF, KGF, TGF-β, VEGF, 4./ to restore the normal bacterial flora by antibiotics, probiotics. However, in spite of these numerous potential targets, the true value and clinical significance of most of the new biologics and molecules are not clear yet.
Similar articles
- Biologic therapy for inflammatory bowel disease.
Ardizzone S, Bianchi Porro G. Ardizzone S, et al. Drugs. 2005;65(16):2253-86. doi: 10.2165/00003495-200565160-00002. Drugs. 2005. PMID: 16266194 Review. - Inflammatory Bowel Disease: Updates on Molecular Targets for Biologics.
Katsanos KH, Papadakis KA. Katsanos KH, et al. Gut Liver. 2017 Jul 15;11(4):455-463. doi: 10.5009/gnl16308. Gut Liver. 2017. PMID: 28486793 Free PMC article. Review. - Biologic targeting in the treatment of inflammatory bowel diseases.
Bosani M, Ardizzone S, Porro GB. Bosani M, et al. Biologics. 2009;3:77-97. Epub 2009 Jul 13. Biologics. 2009. PMID: 19707398 Free PMC article. Retracted. - The bacterial flora in inflammatory bowel disease: current insights in pathogenesis and the influence of antibiotics and probiotics.
Linskens RK, Huijsdens XW, Savelkoul PH, Vandenbroucke-Grauls CM, Meuwissen SG. Linskens RK, et al. Scand J Gastroenterol Suppl. 2001;(234):29-40. doi: 10.1080/003655201753265082. Scand J Gastroenterol Suppl. 2001. PMID: 11768558 Review. - Biologic therapies against inflammatory bowel disease: a dysregulated immune system and the cross talk with gastrointestinal mucosa hold the key.
Dharmani P, Chadee K. Dharmani P, et al. Curr Mol Pharmacol. 2008 Nov;1(3):195-212. doi: 10.2174/1874467210801030195. Curr Mol Pharmacol. 2008. PMID: 20021434 Review.
Cited by
- Reconstruction and Differential Expression Profiling Core Target Analyses of the circRNA-miRNA-mRNA Network Based on Competitive Endogenous RNAs in Ulcerative Colitis.
Xu S, Chen S, Zhang M, An W, Li J, Sun Z, Xu Y. Xu S, et al. Evid Based Complement Alternat Med. 2022 Oct 21;2022:4572181. doi: 10.1155/2022/4572181. eCollection 2022. Evid Based Complement Alternat Med. 2022. PMID: 36310619 Free PMC article. - Impact of intrarectal chromofungin treatment on dendritic cells-related markers in different immune compartments in colonic inflammatory conditions.
Kapoor K, Eissa N, Tshikudi D, Bernstein CN, Ghia JE. Kapoor K, et al. World J Gastroenterol. 2021 Dec 21;27(47):8138-8155. doi: 10.3748/wjg.v27.i47.8138. World J Gastroenterol. 2021. PMID: 35068859 Free PMC article. - Tryptophan Metabolites Along the Microbiota-Gut-Brain Axis: An Interkingdom Communication System Influencing the Gut in Health and Disease.
Bosi A, Banfi D, Bistoletti M, Giaroni C, Baj A. Bosi A, et al. Int J Tryptophan Res. 2020 Jun 11;13:1178646920928984. doi: 10.1177/1178646920928984. eCollection 2020. Int J Tryptophan Res. 2020. PMID: 32577079 Free PMC article. Review. - Endothelial MT1-MMP targeting limits intussusceptive angiogenesis and colitis via TSP1/nitric oxide axis.
Esteban S, Clemente C, Koziol A, Gonzalo P, Rius C, Martínez F, Linares PM, Chaparro M, Urzainqui A, Andrés V, Seiki M, Gisbert JP, Arroyo AG. Esteban S, et al. EMBO Mol Med. 2020 Feb 7;12(2):e10862. doi: 10.15252/emmm.201910862. Epub 2019 Dec 3. EMBO Mol Med. 2020. PMID: 31793743 Free PMC article. - Cost Burden of Crohn's Disease and Ulcerative Colitis in the 10-Year Period Before Diagnosis-A Danish Register-Based Study From 2003-2015.
Vadstrup K, Alulis S, Borsi A, Gustafsson N, Nielsen A, Wennerström ECM, Jørgensen TR, Qvist N, Munkholm P. Vadstrup K, et al. Inflamm Bowel Dis. 2020 Aug 20;26(9):1377-1382. doi: 10.1093/ibd/izz265. Inflamm Bowel Dis. 2020. PMID: 31693731 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Miscellaneous