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34 kDa MOMP of Shigella flexneri promotes TLR2 mediated macrophage activation with the engagement of NF-kappaB and p38 MAP kinase signaling.
Mol Immunol. 2010 May; 47(9):1739-46.MI

Abstract

The 34 kDa major outer membrane protein (MOMP) of Shigella flexneri 2a induces combinatorial expression of TLR2 and TLR6 on peritoneal macrophages of BALB/c mice. Between the two best-characterized TLRs, to date, TLR2 and TLR4, which are chiefly responsible for recognizing majority of bacterial products, TLR2 alone participates in recognition of 34 kDa MOMP. In addition to TLRs, MOMP enhances the mRNA expression of MyD88 and TRAF6 and induces the nuclear translocation of NF-kappaB as well as activates p38 MAP kinase, suggesting the involvement of these molecules in the mechanism of action of MOMP. 34 kDa MOMP also stimulates macrophages, up regulates the surface expression of MHC-II and B7-1 and enhances the production of different cytokines (such as ILp70, TNF-alpha, Il-6) and chemokines (like MIP-1 alpha, MIP-1 beta and RANTES). The ability of the protein in the activation of macrophages, i.e. the induction of nuclear translocation of NF-kappaB and secretion of cytokines are dependent on TLR2 expression as demonstrated by the lack of response by macrophages pre-treated with inhibitory TLR2 mAb. Moreover, it has been found that MOMP induced regulation of TLR2 gene expression is dependent on NF-kappaB and p38 MAP kinase in murine macrophages for the first time. The MOMP induced cytokines and chemokines profile reflect that the protein has the ability to translate innate towards type-1 adaptive response. In conclusion MOMP recognizes by and activates macrophages which may be an initiating event in the antibacterial host response.

Authors+Show Affiliations

Division of Pathophysiology, National Institute of Cholera and Enteric Diseases, P-33, C.I.T. Road, Scheme-XM, Beliaghata, Kolkata 700010, West Bengal, India.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

20347487

Citation

Pore, Debasis, et al. "34 kDa MOMP of Shigella Flexneri Promotes TLR2 Mediated Macrophage Activation With the Engagement of NF-kappaB and P38 MAP Kinase Signaling." Molecular Immunology, vol. 47, no. 9, 2010, pp. 1739-46.
Pore D, Mahata N, Pal A, et al. 34 kDa MOMP of Shigella flexneri promotes TLR2 mediated macrophage activation with the engagement of NF-kappaB and p38 MAP kinase signaling. Mol Immunol. 2010;47(9):1739-46.
Pore, D., Mahata, N., Pal, A., & Chakrabarti, M. K. (2010). 34 kDa MOMP of Shigella flexneri promotes TLR2 mediated macrophage activation with the engagement of NF-kappaB and p38 MAP kinase signaling. Molecular Immunology, 47(9), 1739-46. https://doi.org/10.1016/j.molimm.2010.03.001
Pore D, et al. 34 kDa MOMP of Shigella Flexneri Promotes TLR2 Mediated Macrophage Activation With the Engagement of NF-kappaB and P38 MAP Kinase Signaling. Mol Immunol. 2010;47(9):1739-46. PubMed PMID: 20347487.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 34 kDa MOMP of Shigella flexneri promotes TLR2 mediated macrophage activation with the engagement of NF-kappaB and p38 MAP kinase signaling. AU - Pore,Debasis, AU - Mahata,Nibedita, AU - Pal,Amit, AU - Chakrabarti,Manoj K, Y1 - 2010/03/27/ PY - 2009/12/01/received PY - 2010/02/02/revised PY - 2010/03/03/accepted PY - 2010/3/30/entrez PY - 2010/3/30/pubmed PY - 2010/6/5/medline SP - 1739 EP - 46 JF - Molecular immunology JO - Mol Immunol VL - 47 IS - 9 N2 - The 34 kDa major outer membrane protein (MOMP) of Shigella flexneri 2a induces combinatorial expression of TLR2 and TLR6 on peritoneal macrophages of BALB/c mice. Between the two best-characterized TLRs, to date, TLR2 and TLR4, which are chiefly responsible for recognizing majority of bacterial products, TLR2 alone participates in recognition of 34 kDa MOMP. In addition to TLRs, MOMP enhances the mRNA expression of MyD88 and TRAF6 and induces the nuclear translocation of NF-kappaB as well as activates p38 MAP kinase, suggesting the involvement of these molecules in the mechanism of action of MOMP. 34 kDa MOMP also stimulates macrophages, up regulates the surface expression of MHC-II and B7-1 and enhances the production of different cytokines (such as ILp70, TNF-alpha, Il-6) and chemokines (like MIP-1 alpha, MIP-1 beta and RANTES). The ability of the protein in the activation of macrophages, i.e. the induction of nuclear translocation of NF-kappaB and secretion of cytokines are dependent on TLR2 expression as demonstrated by the lack of response by macrophages pre-treated with inhibitory TLR2 mAb. Moreover, it has been found that MOMP induced regulation of TLR2 gene expression is dependent on NF-kappaB and p38 MAP kinase in murine macrophages for the first time. The MOMP induced cytokines and chemokines profile reflect that the protein has the ability to translate innate towards type-1 adaptive response. In conclusion MOMP recognizes by and activates macrophages which may be an initiating event in the antibacterial host response. SN - 1872-9142 UR - https://www.unboundmedicine.com/medline/citation/20347487/34_kDa_MOMP_of_Shigella_flexneri_promotes_TLR2_mediated_macrophage_activation_with_the_engagement_of_NF_kappaB_and_p38_MAP_kinase_signaling_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0161-5890(10)00080-5 DB - PRIME DP - Unbound Medicine ER -