| First Author | Ochiai T | Year | 2021 |
| Journal | FASEB J | Volume | 35 |
| Issue | 10 | Pages | e21952 |
| PubMed ID | 34555210 | Mgi Jnum | J:317714 |
| Mgi Id | MGI:6844974 | Doi | 10.1096/fj.202101025R |
| Citation | Ochiai T, et al. (2021) Absence of prostacyclin greatly relieves cyclophosphamide-induced cystitis and bladder pain in mice. FASEB J 35(10):e21952 |
| abstractText | 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 (PGI2 ) is produced in bladder tissues, and PGI2 has been shown to play a critical role in bladder homeostasis. PGI2 is biosynthesized from prostaglandin (PG) H2 , the common precursor of PGs, by PGI2 synthase (PTGIS) and is known to also be involved in inflammatory responses. However, little is known about the roles of PTGIS-derived PGI2 in bladder inflammation including CP-induced hemorrhagic cystitis. Using both genetic and pharmacological approaches, we here revealed that PTGIS-derived PGI2 -IP (PGI2 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. |
