PMID- 21637390 OWN - NLM STAT- PubMed-not-MEDLINE DCOM- 20110714 LR - 20211020 IS - 2092-6685 (Electronic) IS - 1598-2629 (Print) IS - 1598-2629 (Linking) VI - 11 IP - 2 DP - 2011 Apr TI - Mycobacterial Heparin-binding Hemagglutinin Antigen Activates Inflammatory Responses through PI3-K/Akt, NF-kappaB, and MAPK Pathways. PG - 123-33 LID - 10.4110/in.2011.11.2.123 [doi] AB - BACKGROUND: Mycobacterium tuberculosis (Mtb) heparin binding hemagglutinin (HBHA) is an Ag known to evoke effective host immune responses during tuberculosis infection. However, the molecular basis of the host immune response to HBHA has not been fully characterized. In this study, we examined the molecular mechanisms by which HBHA can induce the expression of proinflammatory cytokines in macrophages. METHODS: HBHA-induced mRNA and protein levels of proinflammatory cytokines were determined in bone marrow-derived macrophages (BMDMs) using RT-PCR and ELISA analysis. The roles of intracellular signaling pathways for NF-kappaB, PI3-K/Akt, and MAPKs were investigated in macrophage proinflammatory responses after stimulation with HBHA. RESULTS: HBHA robustly activated the expression of mRNA and protein of both TNF-alpha and IL-6, and induced phosphorylation of NF-kappaB, Akt, and MAPKs in BMDMs. Both TNF-alpha and IL-6 production by HBHA was regulated by the NF-kappaB, PI3-K, and MAPK pathways. Furthermore, PI3-K activity was required for the HBHA-induced activation of ERK1/2 and p38 MAPK, but not JNK, pathways. CONCLUSION: These data suggest that mycobacterial HBHA significantly induces proinflammatory responses through crosstalk between the PI3-K and MAPK pathways in macrophages. FAU - Kim, Ki-Hye AU - Kim KH AD - Department of Microbiology, College of Medicine, Chungnam National University, Daejeon 301-747, Korea. FAU - Yang, Chul-Su AU - Yang CS FAU - Shin, A-Rum AU - Shin AR FAU - Jeon, So-Ra AU - Jeon SR FAU - Park, Jeong-Kyu AU - Park JK FAU - Kim, Hwa-Jung AU - Kim HJ FAU - Jo, Eun-Kyeong AU - Jo EK LA - eng PT - Journal Article DEP - 20110430 PL - Korea (South) TA - Immune Netw JT - Immune network JID - 101137270 PMC - PMC3100523 OTO - NOTNLM OT - Heparin-binding hemagglutinin (HBHA) OT - MAPK OT - Macrophages OT - Mycobacterium tuberculosis OT - NF-kappaB OT - PI3-K COIS- The authors have no financial conflict of interest. EDAT- 2011/06/04 06:00 MHDA- 2011/06/04 06:01 PMCR- 2011/04/01 CRDT- 2011/06/04 06:00 PHST- 2011/03/18 00:00 [received] PHST- 2011/04/04 00:00 [revised] PHST- 2011/04/14 00:00 [accepted] PHST- 2011/06/04 06:00 [entrez] PHST- 2011/06/04 06:00 [pubmed] PHST- 2011/06/04 06:01 [medline] PHST- 2011/04/01 00:00 [pmc-release] AID - 10.4110/in.2011.11.2.123 [doi] PST - ppublish SO - Immune Netw. 2011 Apr;11(2):123-33. doi: 10.4110/in.2011.11.2.123. Epub 2011 Apr 30.