Premium
NOS stimulates COX‐1‐mediated barrier function and inhibits COX‐2 in Cryptosporidium infection
Author(s) -
Gookin Jody,
Stauffer Stephen
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.978.3
Subject(s) - nitric oxide synthase , barrier function , lamina propria , cryptosporidium parvum , epithelium , biology , chemistry , immunology , microbiology and biotechnology , nitric oxide , endocrinology , genetics
Cryptosporidium parvum (CP) is a parasite of intestinal epithelium. CP increases intestinal mucosal synthesis of prostaglandins (PG), the majority of which is dependent on nitric oxide synthase (NOS) activity. While PG stimulate Cl‐ secretion and diarrhea in CP infection they also promote epithelial barrier function. We sought to determine the identity and location of COX expression in CP infection and whether barrier function could be ascribed to a single isoform of COX. Expression of COX‐1 and ‐2 were quantified by real time RT‐PCR and immunoblots performed on ileal epithelium and lamina propria from control and CP‐infected piglets. PG synthesis and barrier function were measured in Ussing chambers in the presence of COX‐selective and NOS inhibitors. The role of iNOS in control of COX‐1 and ‐2 expression was investigated by examining the effect of iNOS inhibition on COX expression. CP infection resulted in preservation of COX‐1 and inhibition of COX‐2 expression. While both COX‐1 and COX‐2 contributed to PG synthesis, NOS‐dependent epithelial barrier function was mediated by COX‐1. In contrast, iNOS inhibited epithelial COX‐2 expression in CP infection. We have shown that iNOS‐derived NO mediates the increase in PG synthesis in CP infection and NO donors can exacerbate PG synthesis and diarrhea. By downregulating expression of COX‐2, iNOS may restrain PG synthesis and diarrhea in CP infection.