Vol. 281, Issue 2, G552-G559, August 2001
Developmental variability in expression and regulation of
inducible nitric oxide synthase in rat intestine
Melinda J.
Morin,
Shannon M.
Karr,
Ronald A.
Faris, and
Philip A.
Gruppuso
Department of Pediatrics, Rhode Island Hospital, Brown University
School of Medicine, Providence, Rhode Island 02903
Inducible nitric oxide
synthase (iNOS) may be a key mediator of intestinal injury, which
varies with developmental age. One member of the mitogen-activated
protein kinase (MAPK) family, p38, is involved in the
lipopolysaccharide (LPS)-mediated iNOS induction. The involvement of
p38 MAPK in basal and LPS-induced iNOS expression was examined in the
rat intestine at two developmental ages. Neonatal (4 days postnatal)
and adolescent (15 days postnatal) rats were injected with LPS (5 µg/g ip), a selective p38 inhibitor (SB 203580), or both. Tissue was
removed after 4 h and 6 h for mRNA and protein analysis. iNOS
mRNA and protein were markedly upregulated in the adolescent female
following LPS exposure, whereas males had an attenuated response.
Neonates had a minimal response. SB 203580 suppressed LPS-induced iNOS
mRNA and protein in the ileum, more so in females than in males.
Adolescent ileal p38 activation was constitutively high and
nonresponsive to LPS. Basal and post-LPS p38 phosphorylation was low in
neonatal ileum. We conclude that ileal iNOS expression is
developmentally regulated and influenced by gender and that p38 is
permissive for LPS effect. The developmental regulation of p38 may
contribute to age-dependent variations of intestinal injury.
lipopolysaccharide; p38 mitogen-activated protein kinase
