PgmNr M5093: Combinatorial regulation of Batf and Batf2 in LPS-stimulated and Mycobacterium-infected inflammatory responses.

Authors:
H. Suzuki 1 ; S. Roy 1 ; R. Guler 2,3 ; S. Schmeier 4 ; S. Parihar 2,3 ; M. Ozturk 2,3 ; F. Brombacher 2,3


Institutes
1) RIKEN CLST, Yokohama, JP; 2) ICGEB, Cape Town, SA; 3) Cape Town Univ., Cape Town, SA; 4) Massey Univ., North Shore, NZ.


Abstract:

Basic leucine zipper transcription factor Batf belongs to the activator protein (AP-1) family of transcription factors, consisting of Batf, Batf2 and Batf3, and is a positive regulator of various cellular processes in DCs, T and B cells. During our recent finding that BATF2 induces inflammatory responses in classically activated macrophages, lipopolysaccharide (LPS) or Mycobacterium tuberculosis (Mtb) infection, we found that Batf expression was also induced in LPS-stimulated and Mtb-infected macrophages, but not in IFNγ-activated classical activation. In order to explore BATF function in macrophages, we assessed the effect of Batf knockdown in LPS-stimulated mouse bone marrow-derived macrophages and compared it with that of Batf2 knockdown. We found that BATF and BATF2 regulate different set of genes; the gene ontology analysis revealed that BATF suppresses negative regulators of inflammatory response. Further, Batf2 knockdown up-regulated Batf expression, suggesting that BATF2 is a negative regulator of Batf expression. Taken together with the BATF2 function, our results suggest that BATF plays an important role of augmentation of the inflammatory response in LPS-stimulated macrophages.