Mycobacterial Heparin-binding Hemagglutinin Antigen Activates Inflammatory Responses through PI3-K/Akt, NF-kappaB, and MAPK Pathways.
- Author:
Ki Hye KIM
1
;
Chul Su YANG
;
A Rum SHIN
;
So Ra JEON
;
Jeong Kyu PARK
;
Hwa Jung KIM
;
Eun Kyeong JO
Author Information
- Publication Type:Original Article
- Keywords: Mycobacterium tuberculosis; Heparin-binding hemagglutinin (HBHA); Macrophages; MAPK; PI3-K; NF-kappaB
- MeSH: Cytokines; Enzyme-Linked Immunosorbent Assay; Hemagglutinins; Heparin; Interleukin-6; Lectins; Macrophages; Mycobacterium tuberculosis; NF-kappa B; p38 Mitogen-Activated Protein Kinases; Phosphorylation; RNA, Messenger; Tuberculosis; Tumor Necrosis Factor-alpha
- From:Immune Network 2011;11(2):123-133
- CountryRepublic of Korea
- Language:English
- Abstract: 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.
