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Papers of the Week


Papers: 18 Sep 2021 - 24 Sep 2021


Animal Studies


2021 Oct


FASEB J


35


10

Absence of prostacyclin greatly relieves cyclophosphamide-induced cystitis and bladder pain in mice.

Authors

Ochiai T, Sasaki Y, Yokoyama C, Kuwata H, Hara S
FASEB J. 2021 Oct; 35(10):e21952.
PMID: 34555210.

Abstract

Cyclophosphamide (CP) has been widely used in the treatment of various malignancies and autoimmune diseases, but acrolein, a byproduct of CP, causes severe hemorrhagic cystitis as the major side effect of CP. On the other hand, a large amount of prostacyclin (PGI ) is produced in bladder tissues, and PGI has been shown to play a critical role in bladder homeostasis. PGI is biosynthesized from prostaglandin (PG) H , the common precursor of PGs, by PGI synthase (PTGIS) and is known to also be involved in inflammatory responses. However, little is known about the roles of PTGIS-derived PGI in bladder inflammation including CP-induced hemorrhagic cystitis. Using both genetic and pharmacological approaches, we here revealed that PTGIS-derived PGI -IP (PGI receptor) signaling exacerbated CP-induced bladder inflammatory reactions. Ptgis deficiency attenuated CP-induced vascular permeability and chemokine-mediated neutrophil migration into bladder tissues and then suppressed hemorrhagic cystitis. Treatment with RO1138452, an IP selective antagonist, also suppressed CP-induced cystitis. We further found that cystitis-related nociceptive behavior was also relieved in both Ptgis mice and RO1138452-treated mice. Our findings may provide new drug targets for bladder inflammation and inflammatory pain in CP-induced hemorrhagic cystitis.