Bacterial ligand stimulates TLR2-dependent chemokines of colon cell

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.