Myeloid cell mPGES-1 mediates inflammatory pain hypersensitivity in mice
Chen L, Yang G, Cormode DP, Saigal A, Madhavan S, Mazaleuskaya LL, Grant GR, FitzGerald GA, Grosser T (2020)
bioRxiv.
Preprint | Englisch
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Autor*in
Chen, Lihong;
Yang, Guangrui;
Cormode, David P.;
Saigal, Ashmita;
Madhavan, Shravanthi;
Mazaleuskaya, Liudmila L.;
Grant, Gregory R.;
FitzGerald, Garret A.;
Grosser, TiloUniBi ![](https://pub.uni-bielefeld.de/images/icon_orcid.png)
![](https://pub.uni-bielefeld.de/images/icon_orcid.png)
Abstract / Bemerkung
Nonsteroidal anti-inflammatory drugs (NSAIDs) relieve inflammatory pain by predominant suppression of cyclooxygenase-2 derived prostaglandin (PG) E2. Innate immune cells contribute to inflammatory pain hypersensitivity and may be an attractive target for novel non-addictive approaches to pain management. We studied the contribution of PGE2 produced by myeloid cell microsomal prostaglandin E synthase -1 (mPGES-1) to peripheral inflammation and hyperalgesia in mice. Selective deletion of mPGES-1 in myeloid cells by crossing LysM-Cre mice with mPGES-1flox/flox mice (Mac-mPGES-1-KO) resulted in significantly reduced mechanical and thermal hyperalgesia in complete Freund{\textquoteright}s adjuvant (CFA)-evoked hind paw inflammation, zymosan-induced peri-articular inflammation and collagen II antibody-induced arthritis models. Systemic COX-2 inhibition or myeloid cell specific COX-2 deletion (by crossing LysM-Cre with COX-2 flox/flox mice) recapitulated reduction of CFA-induced inflammation and hyperalgesia. In contrast, deletion of mPGES-1 in neurons and glial cells by crossing mPGES-1flox/flox mice with Nestin-Cre mice had no detectable effect on inflammatory pain hypersensitivity. While macrophage recruitment was unaltered, tissue concentrations of PGE2, IL-1β and TNFα were significantly reduced in Mac-mPGES-1-KO paw tissues following CFA induction. Our results demonstrate that myeloid cell mPGES-1 is the dominant source of PGE2 in inflammatory pain hypersensitivity. Targeting myeloid cell mPGES-1 may afford a novel approach to inflammatory pain therapy.
Erscheinungsjahr
2020
Zeitschriftentitel
bioRxiv
Page URI
https://pub.uni-bielefeld.de/record/2990276
Zitieren
Chen L, Yang G, Cormode DP, et al. Myeloid cell mPGES-1 mediates inflammatory pain hypersensitivity in mice. bioRxiv. 2020.
Chen, L., Yang, G., Cormode, D. P., Saigal, A., Madhavan, S., Mazaleuskaya, L. L., Grant, G. R., et al. (2020). Myeloid cell mPGES-1 mediates inflammatory pain hypersensitivity in mice. bioRxiv. https://doi.org/10.1101/2020.01.31.929422
Chen, Lihong, Yang, Guangrui, Cormode, David P., Saigal, Ashmita, Madhavan, Shravanthi, Mazaleuskaya, Liudmila L., Grant, Gregory R., FitzGerald, Garret A., and Grosser, Tilo. 2020. “Myeloid cell mPGES-1 mediates inflammatory pain hypersensitivity in mice”. bioRxiv.
Chen, L., Yang, G., Cormode, D. P., Saigal, A., Madhavan, S., Mazaleuskaya, L. L., Grant, G. R., FitzGerald, G. A., and Grosser, T. (2020). Myeloid cell mPGES-1 mediates inflammatory pain hypersensitivity in mice. bioRxiv.
Chen, L., et al., 2020. Myeloid cell mPGES-1 mediates inflammatory pain hypersensitivity in mice. bioRxiv.
L. Chen, et al., “Myeloid cell mPGES-1 mediates inflammatory pain hypersensitivity in mice”, bioRxiv, 2020.
Chen, L., Yang, G., Cormode, D.P., Saigal, A., Madhavan, S., Mazaleuskaya, L.L., Grant, G.R., FitzGerald, G.A., Grosser, T.: Myeloid cell mPGES-1 mediates inflammatory pain hypersensitivity in mice. bioRxiv. (2020).
Chen, Lihong, Yang, Guangrui, Cormode, David P., Saigal, Ashmita, Madhavan, Shravanthi, Mazaleuskaya, Liudmila L., Grant, Gregory R., FitzGerald, Garret A., and Grosser, Tilo. “Myeloid cell mPGES-1 mediates inflammatory pain hypersensitivity in mice”. bioRxiv (2020).
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