title: Mycobacterial Heparin-binding Hemagglutinin Antigen Activates Inflammatory Responses through PI3-K/Akt, NF-κB, and MAPK Pathways.
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-κB, 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-α and IL-6, and induced phosphorylation of NF-κB, Akt, and MAPKs in BMDMs. Both TNF-α and IL-6 production by HBHA was regulated by the NF-κB, 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.
  
  
  CONCLUSIONS
  These data suggest that mycobacterial HBHA significantly induces proinflammatory responses through crosstalk between the PI3-K and MAPK pathways in macrophages.
authors.affiliation: Department of Microbiology, College of Medicine, Chungnam National University, Daejeon 301-747, Korea.
authors.forename: Ki-Hye
authors.initials: KH
authors.lastname: Kim
authors.forename: Chul-Su
authors.initials: CS
authors.lastname: Yang
authors.forename: A-Rum
authors.initials: AR
authors.lastname: Shin
authors.forename: So-Ra
authors.initials: SR
authors.lastname: Jeon
authors.forename: Jeong-Kyu
authors.initials: JK
authors.lastname: Park
authors.forename: Hwa-Jung
authors.initials: HJ
authors.lastname: Kim
authors.forename: Eun-Kyeong
authors.initials: EK
authors.lastname: Jo