title: SerpinB2 deficiency modulates Th1⁄Th2 responses after schistosome infection.
abstract: SerpinB2, also known as plasminogen activator inhibitor type-2, is a major product of macrophages and is upregulated during many infections. Although SerpinB2 inhibits urokinase plasminogen activator in vitro, evidence that this represents its physiological role in vivo is not compelling. We have recently shown that SerpinB2-/-mice generate enhanced Th1 responses after immunization with a Th1 immunogen. Herein,we show that Schistosoma japonicum granulomas induced liver SerpinB2 mRNA expression by >600-fold in wild-type mice. In SerpinB2-/- mice, worm and egg burden, and granuloma number and volume were unaffected. However, granulomas in these mice were associated with reduced fibrosis (as determined by Sirius red staining and image analysis) and increased iNOS, IL-6, IL-10 and TNFa and decreased Arg 1 and IL-13 mRNA expression. SerpinB2-/- mice immunized with soluble egg antigen (SEA) also showed reduced levels of SEA-specific IgG1. SerpinB2 deficiency thus promoted certain Th1 and reduced certain Th2 responses in response to this Th2 immunogen.
authors.affiliation: Queensland Institute of Medical Research, Brisbane, Qld., Australia.
authors.forename: W A
authors.initials: WA
authors.lastname: Schroder
authors.forename: J
authors.initials: J
authors.lastname: Gardner
authors.forename: T T
authors.initials: TT
authors.lastname: Le
authors.forename: M
authors.initials: M
authors.lastname: Duke
authors.forename: M L
authors.initials: ML
authors.lastname: Burke
authors.forename: M K
authors.initials: MK
authors.lastname: Jones
authors.forename: D P
authors.initials: DP
authors.lastname: McManus
authors.forename: A
authors.initials: A
authors.lastname: Suhrbier
mesh_terms: D000818:Animals; D001119:Arginase / Q000096:biosynthesis; D016207:Cytokines / Q000096:biosynthesis; D020869:Gene Expression Profiling; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis; D017396:Plasminogen Activator Inhibitor 2 / Q000172:deficiency / Q000502:physiology*; D012549:Schistosoma japonicum / Q000276:immunology*; D012554:Schistosomiasis japonica / Q000276:immunology* / Q000469:parasitology / Q000473:pathology; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*
chemical_list: D016207:Cytokines; D017396:Plasminogen Activator Inhibitor 2; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; C544448:Arg1 protein, mouse; D001119:Arginase