Expression of fibrogenic cytokines in rat small intestine after fractionated irradiation.
The molecular and cellular mechanisms that regulate the radiation-induced fibrotic response in the intestine are not known. In addition to increased amounts of connective tissue, inflammatory cell aggregates are often found, especially in conjunction with acute or chronic mucosal ulcerations. These inflammatory cells are a major source of cytokines that influence connective tissue metabolism. Hence, a possible link may exist between the cellular inflammatory response and fibrosis. This preclinical study examined the influence of fractionated irradiation on the expression of three inflammatory/fibrogenic cytokines in rat small intestine. A rat intestinal transposition model was used for localized fractionated irradiation of a 3-4-cm segment of small bowel. Fifty-nine male Sprague-Dawley rats were irradiated or sham irradiated with 9 daily fractions of 5.2 Gy. Expression of Interleukin 1 alpha (IL-1 alpha), Transforming growth factor beta 1 (TGF-beta 1), and Platelet derived growth factor-AA (PDGF-AA) was assessed by immunohistochemistry. Irradiated and unirradiated intestine was examined 24 h, 14 days, and 26 weeks after completion of irradiation. Unirradiated intestine exhibited immunohistochemical expression of IL-1 alpha, TGF-beta 1 and PDGF-AA that conformed to known staining patterns in normal tissue. Irradiated intestine showed increased expression of all three cytokines at all assessment times. The increased cytokine expression correlated with fibrosis and inflammatory cell infiltrates in irradiated intestine. This was particularly evident in areas with mucosal ulcerations. Fractionated irradiation of small intestine elicits increased expression of IL-1 alpha, TGF-beta 1, and PDGF-AA in areas of acute and chronic radiation injury.(ABSTRACT TRUNCATED AT 250 WORDS)
Langberg
C W
CW
Department of Surgery, University of Arkansas for Medical Sciences, Little Rock 72205.
Hauer-Jensen
M
M
Sung
C C
CC
Kane
C J
CJ
D000818:Animals; D016207:Cytokines / Q000378:metabolism* / Q000528:radiation effects*; D004730:Endothelium, Vascular / Q000378:metabolism / Q000473:pathology / Q000528:radiation effects; D004848:Epithelium / Q000378:metabolism / Q000473:pathology / Q000528:radiation effects; D005109:Extracellular Matrix / Q000378:metabolism / Q000528:radiation effects; D005355:Fibrosis; D015870:Gene Expression / Q000528:radiation effects; D007375:Interleukin-1 / Q000378:metabolism / Q000528:radiation effects; D007410:Intestinal Diseases / Q000378:metabolism / Q000473:pathology; D007413:Intestinal Mucosa / Q000378:metabolism / Q000473:pathology / Q000528:radiation effects; D007421:Intestine, Small / Q000378:metabolism / Q000473:pathology / Q000528:radiation effects*; D008297:Male; D009130:Muscle, Smooth / Q000378:metabolism / Q000473:pathology / Q000528:radiation effects; D010982:Platelet-Derived Growth Factor / Q000378:metabolism / Q000528:radiation effects; D011829:Radiation Dosage; D011833:Radiation Injuries, Experimental / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D016212:Transforming Growth Factor beta / Q000378:metabolism / Q000528:radiation effects; D014456:Ulcer / Q000378:metabolism / Q000473:pathology
D016207:Cytokines; D007375:Interleukin-1; D010982:Platelet-Derived Growth Factor; D016212:Transforming Growth Factor beta; C075278:platelet-derived growth factor A