| Autor: |
Sullivan, Graeme P., Davidovich, Pavel, Muñoz-Wolf, Natalia, Ward, Ross W., Hernandez Santana, Yasmina E., Clancy, Danielle M., Gorman, Aoife, Najda, Zaneta, Turk, Boris, Walsh, Patrick T., Lavelle, Ed C., Martin, Seamus J. |
| Zdroj: |
Science Immunology; 2022, Vol. 7 Issue 78, p1-15, 15p, 7 Graphs |
| Abstrakt: |
Interleukin-1 (IL-1) family cytokines are key barrier cytokines that are typically expressed as inactive, or partially active, precursors that require proteolysis within their amino termini for activation. IL-37 is an enigmatic member of the IL-1 family that has been proposed to be activated by caspase-1 and to exert anti-inflammatory activity through engagement of the IL-18R and SIGIRR. However, here we show that the longest IL-37 isoform, IL-37b, exhibits robust proinflammatory activity upon amino-terminal proteolysis by neutrophil elastase or cathepsin S. In sharp contrast, caspase-1 failed to process or activate IL-37 at concentrations that robustly activated its canonical substrate, IL-1β. IL-37 and IL-36 exhibit high structural homology, and, consistent with this, a K53-truncated form of IL-37, mimicking the cathepsin S–processed form of this cytokine,was found to exert its proinflammatory effects via IL-36 receptor engagement and produced an inflammatory signature practically identical to IL-36. Administration of K53-truncated IL-37b intraperitoneally into wild-type mice also elicited an inflammatory response that was attenuated in IL-36R−/− animals. These data demonstrate that, in common with other IL-1 family members, mature IL-37 can also elicit proinflammatory effects upon processing by specific proteases. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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