Article
- The EMBO Journal (2006) 25, 2878 - 2888
- doi:10.1038/sj.emboj.7601170
Published online: 8 June 2006
Subject Category:
IL-6 and IL-12 specifically regulate the expression of Rab5 and Rab7 via distinct signaling pathways
Malavika Bhattacharya1, Namrata Ojha1, Sunil Solanki2, Chinmay K Mukhopadhyay2, Richa Madan1, Nitin Patel1, Ganga Krishnamurthy1, Senthil Kumar1, Sandip K Basu1 and Amitabha Mukhopadhyay1
- National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi, India
- Center for Molecular Medicine, Jawaharlal Nehru University, New Delhi, India
Correspondence to:
Amitabha Mukhopadhyay, Cell Biology Laboratory, National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi 110067, India. Tel.: +91 11 26703536, +91 11 26703596; Fax: +91 11 26717104; E-mail: amitabha@nii.res.in
Received 14 December 2005; Accepted 5 May 2006
Abstract
Recent studies have shown that phagosome maturation depends on the balance between pro-inflammatory and anti-inflammatory cytokines, indicating that cytokine modulates phagosome maturation. However, the mechanism of cytokine-mediated modulation of intracellular trafficking remains to be elucidated. Here, we have shown that treatment of macrophages with IL-6 specifically induce the expression of Rab5 through the activation of extracellular signal-regulated kinase, whereas IL-12 exclusively upregulate the expression of Rab7 through the activation of p38 MAPK. We have cloned the 5'-flanking regions of the rab5c or rab7 into the promoterless reporter vector. Our results have shown that cells transfected with rab5c chimera are transactivated by IL-6, and IL-12 specifically transactivates cells containing rab7 chimera. Moreover, our results also show that IL-12 induces lysosomal transport, whereas IL-6 stimulates the fusion between early compartments in macrophages and accordingly modulates Salmonella trafficking and survival in macrophages. This is the first demonstration showing that cytokine differentially regulates endocytic trafficking by controlling the expression of appropriate Rab GTPase, and provides insight into the mechanism of cytokine-mediated regulation of intracellular trafficking.
Keywords:
- cytokines,
- endocytosis,
- gene regulation,
- Rab GTPase,
- trafficking
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