Platelet-activating factor receptor mRNA is localized in eosinophils and epithelial cells in rat small intestine: regulation by dexamethasone and gut flora.
Platelet-activating factor (PAF) is a potent mediator involved in bowel injury. We investigated PAF receptor transcription and its mRNA localization in the small intestine of normal (conventionally fed) and germ-free rats, by competitive polymerase chain reaction (PCR) and in situ hybridization. A dose of PAF (1.5 microg/kg, i.v.) insufficient to cause gross bowel injury was injected into rats. Some rats were pretreated with dexamethasone (1 mg/kg). We found: (1) PAF receptor (PAF-R) mRNA localized predominantly in lamina propria eosinophils and in epithelial cells; (2) PAF increased PAF-receptor signals in the epithelial cells; (3) Dexamethasone depleted eosinophils in the intestine and markedly decreased PAF-receptor transcripts; the response to PAF was also weaker than control rats; (4) Germ-free rats had less PAF-R mRNA than normal rats, and showed a weaker response to PAF than conventionally fed rats. Thus, we conclude: (1) PAF receptor mRNA is constitutively expressed in the epithelium and in lamina propria eosinophils in the intestine. (2) PAF-R transcription is up-regulated by PAF and gut flora, mostly in the epithelium. (3) PAF-R transcription is down-regulated by glucocorticoids, mainly as a result of eosinophil depletion. These results suggest a functional role for PAF receptors both in host defence and the inflammatory response in the small intestine.
Wang
H
H
Department of Pathology, Children's Memorial Hospital, Northwestern University Medical School, Chicago, IL 60614, USA.
Tan
X
X
Chang
H
H
Huang
W
W
Gonzalez-Crussi
F
F
Hsueh
W
W
D000818:Animals; D003907:Dexamethasone / Q000494:pharmacology; D004804:Eosinophils / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects*; D005856:Germ-Free Life; D005938:Glucocorticoids / Q000494:pharmacology; D017403:In Situ Hybridization; D007413:Intestinal Mucosa / Q000378:metabolism; D007421:Intestine, Small / Q000378:metabolism* / Q000382:microbiology; D008297:Male; D010972:Platelet Activating Factor / Q000378:metabolism / Q000494:pharmacology*; D010980:Platelet Membrane Glycoproteins / Q000235:genetics* / Q000378:metabolism; D016133:Polymerase Chain Reaction / Q000379:methods; D012333:RNA, Messenger / Q000235:genetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled
D005938:Glucocorticoids; D010972:Platelet Activating Factor; D010980:Platelet Membrane Glycoproteins; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; C039351:platelet activating factor receptor; D003907:Dexamethasone