Sharma, Gaurav and Dutta, Rajesh Kumar and Khan, Mohammad Aslam and Ishaq, Mohammad and Sharma, Kapil and Malhotra, Himanshu and Majumdar, Sekhar (2014) IL-27 inhibits IFN-γ induced autophagy by concomitant induction of JAK/PI3 K/Akt/mTOR cascade and up-regulation of Mcl-1 in Mycobacterium tuberculosis H37Rv infected macrophages. The international journal of biochemistry & cell biology, 55. pp. 335-47. ISSN 1878-5875
Full text not available from this repository. (Request a copy)Abstract
Interleukin-27 (IL-27), a key immunoregulatory cytokine plays an important role in host response to mycobacterial infection as neutralization of IL-27 augments intracellular killing of mycobacteria. Autophagy has a pivotal role in host immunity and is regulated by various cytokines. Here, we report that IL-27 inhibits IFN-γ and starvation induced autophagy and as a result blocks phagosome maturation and promotes intracellular survival of Mycobacterium tuberculosis H37Rv. Addition of exogenous IL-27 induces the activation of mTOR through JAK/PI3 K pathway and inhibits IFN-γ stimulated autophagy. Furthermore, blockade of JAKs obstructs the inhibitory effect of IL-27 on IFN-γ induced autophagy. Besides this, IL-27 also up-regulates Mcl-1 through PI3 K pathway. We further show that in mTOR or Mcl-1 silenced THP-1 cells, IL-27 could no longer inhibit IFN-γ mediated autophagy in M. tuberculosis H37Rv infected cells. Altogether, our study demonstrates that IL-27 by concurrent activation of JAK/PI3 K/Akt/mTOR cascade as well as up-regulation of Mcl-1 inhibits IFN-γ induced autophagy and elimination of intracellular mycobacteria in macrophages.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | Autophagy; IFN-γ; IL-27; Mycobacteria |
| Depositing User: | Dr. K.P.S.Sengar |
| Date Deposited: | 09 Feb 2015 08:14 |
| Last Modified: | 09 Feb 2015 08:14 |
| URI: | http://crdd.osdd.net/open/id/eprint/1550 |
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