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Curcumin attenuates IL-17A mediated pulmonary SMAD dependent and non-dependent mechanism during acute lung injury in vivo

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Abstract

Acute lung injury (ALI) is a pathologic condition responsible for incurable human chronic respiratory diseases. Recent studies have shown the involvement of the glycoprotein, IL17A secreted by IL-17 producing cells in chronic inflammation. The current investigation was carried out to study the IL-17A mediated activation of SMAD and non- SMAD signaling in alveolar epithelial cells and to assess the putative modulatory role of curcumin. C57BL/6 mice were exposed to IL-17A and curcumin was administered as an intervention to modulate the IL-17A-induced alveolar damage. Techniques like Immunofluorescence and real-time PCR were used. We found elevated expression of IL-17A and IL-17A—associated signaling pathways to be activated in mice lung tissues. Curcumin intervention in vivo promoted the resolution of IL-17A-induced ALI and attenuated pulmonary damage. Increase phosphorylation of non- SMAD proteins like P-EGFR, P-STAT-1, STAT-3, P-JAK-1/2, P-JNK, and also SMAD proteins like P- SMAD 2/3 and TGF-β1 was encountered upon IL-17A exposure, while curcumin intervention reversed the protein expression levels. Curcumin was found to block mRNA expressions of non- SMAD genes EGFR, JNK-1, JAK1, JAK2, STAT-1, STAT-3, MAPK14, also of TGF-β1 and SMAD genes like SMAD 2, SMAD 3. However, mRNA expressions of SMAD 6 and SMAD 7 were increased upon curcumin intervention. Our study indicates that IL-17A participates in the development of ALI in both SMAD dependent and independent manner and the IL-17A signaling components were effectively controlled by curcumin, suggesting probable anti-inflammatory use of curcumin during ALI.

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Acknowledgements

This work is supported by Department of Biotechnology (DBT) Grant (BT/PR25198/MED/30/1896/2017) and Yenepoya (Deemed to be University). Ms Sadiya Bi Shaikh extends her gratitude to Yenepoya Research Centre Yenepoya (Deemed to be University) for Senior Research Fellow (SRF) fellowship and for providing all the instrumentation facilities. All the authors acknowledge Dr. Mahesh M Gouda for his help in animal experiments. The authors would like to acknowledge Stem cells and the Regenerative Medicine Centre (SCRMC), Yenepoya Research Centre, Yenepoya (Deemed to be University) for EVOS-M5000 microscope (Invitrogen) facility.

Funding

The authors would like to thank the Department of Biotechnology (DBT) Grant (BT/PR25198/MED/30/1896/2017) & Yenepoya (Deemed to be University) for providing financial support and online library resources for writing this manuscript.

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Authors and Affiliations

  1. Yenepoya Research Centre, Yenepoya (Deemed To Be University), Deralakatte, Mangalore, Karnataka, 575 018, India

    Sadiya Bi Shaikh & Yashodhar Prabhakar Bhandary

  2. Department of Biosciences, Mangalore University, Konaje, Karnataka, 574199, India

    Sinchana G. Bhat

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  1. Sadiya Bi Shaikh
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  2. Sinchana G. Bhat
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  3. Yashodhar Prabhakar Bhandary
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Correspondence to Yashodhar Prabhakar Bhandary.

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Authors declare no conflict of interest financially or otherwise.

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CPCSEA and Institutional animal ethics committee, Yenepoya University, India, the animal experiments were carried out (YU/IAEC/10/2019).

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No humans were used in this study. Animal care was done as per the guidelines of the Committee for Control and Supervision of Experiments on Animals.

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Shaikh, S.B., Bhat, S.G. & Bhandary, Y.P. Curcumin attenuates IL-17A mediated pulmonary SMAD dependent and non-dependent mechanism during acute lung injury in vivo. Mol Biol Rep 47, 5643–5649 (2020). https://doi.org/10.1007/s11033-020-05587-0

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