Interleukin-8 and hIRH (SDF1-alpha/PBSF) mRNA expression and histological activity index in patients with chronic hepatitis C.
Recombinant human intercrine reduced in hepatomas (hIRH)/stromal cell-derived factor 1 (SDF1-alpha)/pre-B-cell growth-stimulating factor (PBSF), a new chemokine, exhibits an in vitro chemotaxis to neutrophils and a mixed in vivo chemotactic activity to neutrophils, lymphocytes, and monocytes in a rat intradermal injection model. We have investigated the messenger RNA (mRNA) expression of interleukin-8 (IL-8) and hIRH, in chronic hepatitis C of differing severity. Levels of expression of IL-8 and hIRH mRNA obtained from 37 human liver biopsy samples were measured by reverse-transcription and semiquantitative polymerase chain reaction (RT-PCR) amplification. We examined the correlation between mRNA expression and components of the histological activity index (HAI). Patients with HAI > or = 8 had a significantly higher corrected IL-8 mRNA expression ratio (0.24 +/- 0.13 [mean +/- SD]; n = 20) than those with HAI < or = 7 (0.05 < or = 0.03; n = 17; P < .0001). Additionally, IL-8 mRNA expression was strongly associated with the severity of portal inflammation (PI) (high PI vs. low PI, 0.22 +/- 0.14 vs. 0.05 +/- 0.04; P < .0001) and with the presence of bile duct lesions (0.29 +/- 0.15 vs. 0.11 +/- 0.1; P < .01). In contrast, hIRH mRNA expression was not associated with the total HAI, any components of the HAI, or bile duct inflammation or injury. These results suggest that hIRH, although having the -CXC-, alpha chemokine motif, and exhibiting in vivo and in vitro inflammatory activity as does IL-8, plays a different role from IL-8 in hepatic inflammation and injury. IL-8 expression is directly associated with inflammation in patients with chronic hepatitis C, while hIRH expression does not correlate with histopathological severity of inflammation.
Shimoda
K
K
Department of Medicine, University of Massachusetts Medical Center, Worcester 01655-0310, USA.
Begum
N A
NA
Shibuta
K
K
Mori
M
M
Bonkovsky
H L
HL
Banner
B F
BF
Barnard
G F
GF
D000818:Animals; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000235:genetics* / Q000494:pharmacology; D002630:Chemotactic Factors / Q000494:pharmacology; D002634:Chemotaxis, Leukocyte / Q000502:physiology; D019698:Hepatitis C, Chronic / Q000378:metabolism*; D006520:Hepatitis, Animal / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D016209:Interleukin-8 / Q000235:genetics*; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D011994:Recombinant Proteins
C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; D002630:Chemotactic Factors; D016209:Interleukin-8; D012333:RNA, Messenger; D011994:Recombinant Proteins