Oxicam-type non-steroidal anti-inflammatory drugs inhibit NPR1-mediated salicylic acid pathway.

Abstract

Nonsteroidal anti-inflammatory drugs (NSAIDs), including salicylic acid (SA), target mammalian cyclooxygenases. In plants, SA is a defense hormone that regulates NON-EXPRESSOR OF PATHOGENESIS RELATED GENES 1 (NPR1), the master transcriptional regulator of immunity-related genes. We identify that the oxicam-type NSAIDs tenoxicam (TNX), meloxicam, and piroxicam, but not other types of NSAIDs, exhibit an inhibitory effect on immunity to bacteria and SA-dependent plant immune response. TNX treatment decreases NPR1 levels, independently from the proposed SA receptors NPR3 and NPR4. Instead, TNX induces oxidation of cytosolic redox status, which is also affected by SA and regulates NPR1 homeostasis. A cysteine labeling assay reveals that cysteine residues in NPR1 can be oxidized in vitro, leading to disulfide-bridged oligomerization of NPR1, but not in vivo regardless of SA or TNX treatment. Therefore, this study indicates that oxicam inhibits NPR1-mediated SA signaling without affecting the redox status of NPR1.

Department

Description

Provenance

Citation

Published Version (Please cite this version)

10.1038/s41467-021-27489-w

Publication Info

Ishihama, Nobuaki, Seung-Won Choi, Yoshiteru Noutoshi, Ivana Saska, Shuta Asai, Kaori Takizawa, Sheng Yang He, Hiroyuki Osada, et al. (2021). Oxicam-type non-steroidal anti-inflammatory drugs inhibit NPR1-mediated salicylic acid pathway. Nature communications, 12(1). p. 7303. 10.1038/s41467-021-27489-w Retrieved from https://hdl.handle.net/10161/26268.

This is constructed from limited available data and may be imprecise. To cite this article, please review & use the official citation provided by the journal.

Scholars@Duke

He

Sheng-Yang He

Benjamin E. Powell Distinguished Professor of Biology

Interested in the fascinating world of plants, microbes or inter-organismal communication and co-evolution? Please contact Prof. Sheng-Yang He (shengyang.he@duke.edu; hes@msu.edu).

Millions of years of co-evolution between plants and microbes have resulted in an intricate web of attack, counter-attack, decoy, and hijacking mechanisms in biology. Moreover, co-evolution between plants and microbes is greatly impacted by ongoing climate change. In our lab, we probe “host-microbe-climate” interactions to answer the following fundamental questions: (1) How do microbial pathogens infect a susceptible host? (2) How do plants select beneficial microbiomes to ensure health? (3) How do climate conditions impact disease and immunity?      

We use contemporary methods to address these questions, including those commonly used in molecular genetics, genomics, biochemistry, cell biology, bioinformatics, microbiology, plant biology, co-evolution and infectious disease biology.    


Unless otherwise indicated, scholarly articles published by Duke faculty members are made available here with a CC-BY-NC (Creative Commons Attribution Non-Commercial) license, as enabled by the Duke Open Access Policy. If you wish to use the materials in ways not already permitted under CC-BY-NC, please consult the copyright owner. Other materials are made available here through the author’s grant of a non-exclusive license to make their work openly accessible.