title: Bacterial ligand stimulates TLR2-dependent chemokines of colon cell.
abstract: Shigella spp. are known to penetrate the colonic epithelial cells causing shigellosis, which results in production of convalescent antibodies against porin, the surface exposed major outer membrane protein. Porin has been categorized as primarily TLR2-ligand and here we validated its signaling procedure in colonic INT-407 cells simulating the host scenario. Porin up-regulated TLR2 and -6 followed by TLR2·MYD88 complex formation suggesting direct involvement of MYD88 for downstream signaling. Translocation of NF-κB p65 and p50 subunits on to the nucleus indicates involvement of the transcription factor in signaling. Porin-induced TLR signaling specifically stimulated the pro-inflammatory chemokine panel comprising of MIP-1α, MCP-1 and IL-8. Inhibition studies of TLR2 and NF-κB led to abrogation of the pro-inflammatory chemokine response, showing TLR-dependent signaling through NF-κB regulate gut activity. This work elucidates TLR2 not only scans pathogen-associated molecule but also has a direct role in maneuvering colon cell response.
authors.affiliation: Division of Immunology, National Institute of Cholera and Enteric Diseases, Kolkata, India.
authors.forename: Subhadeep
authors.initials: S
authors.lastname: Mukherjee
authors.affiliation: Division of Immunology, National Institute of Cholera and Enteric Diseases, Kolkata, India.
authors.forename: Debolina
authors.initials: D
authors.lastname: Sinha
authors.affiliation: Division of Immunology, National Institute of Cholera and Enteric Diseases, Kolkata, India.
authors.forename: Amlan Kanti
authors.initials: AK
authors.lastname: Ghosh
authors.affiliation: Division of Immunology, National Institute of Cholera and Enteric Diseases, Kolkata, India. Electronic address: shigellaporin@yahoo.com.
authors.forename: Tapas
authors.initials: T
authors.lastname: Biswas
mesh_terms: D001419:Bacteria / Q000378:metabolism*; D002460:Cell Line; D018925:Chemokines / Q000096:biosynthesis*; D003106:Colon / Q000166:cytology* / Q000378:metabolism*; D018836:Inflammation Mediators; D016209:Interleukin-8 / Q000378:metabolism; D042541:Intracellular Space / Q000378:metabolism; D008024:Ligands; D053594:Myeloid Differentiation Factor 88; D016328:NF-kappa B / Q000378:metabolism; D018272:Porins / Q000378:metabolism; D021381:Protein Transport; D015398:Signal Transduction; D051195:Toll-Like Receptor 2 / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D018925:Chemokines; D018836:Inflammation Mediators; D016209:Interleukin-8; D008024:Ligands; D053594:Myeloid Differentiation Factor 88; D016328:NF-kappa B; D018272:Porins; D051195:Toll-Like Receptor 2
keywords: Colon cell; Innate response; Porin; Signal transduction; Toll-like receptor 2