Neutrophil chemoattractant 2 beta regulates expression of the Reg gene in injured gastric mucosa in rats.
OBJECTIVE
Regenerating (Reg) protein has a trophic effect on gastric mucosal cells. We have shown that Reg gene expression is increased in enterochromaffin-like (ECL) cells during the healing of damaged gastric mucosa around mucosal erosion. This study was designed to explore the stimulants of Reg expression during the healing of gastric mucosal damage.


METHODS
Time course changes of the expression of genes for various proinflammatory cytokines and Reg were investigated after induction of gastric mucosal lesions in rats. The direct effect of proinflammatory cytokines on Reg gene expression and Reg protein production were investigated in vitro using counterflow elutriation-enriched rat ECL cells. CXC receptor 2 (CXCR-2) expression was investigated in ECL cells by reverse-transcription polymerase chain reaction. Reg gene expression was also investigated in rats treated by the neutralizing antibody of cytokine-induced neutrophil chemoattractant (CINC-2 beta).


RESULTS
During healing, the gene expression of several proinflammatory cytokines and Reg was markedly augmented. Among the proinflammatory cytokines, CINC-2 beta is the only cytokine in which augmented expression preceded the increase of Reg gene expression. In rats treated with CINC-2 beta neutralizing antibody, the augmentation of Reg gene expression was significantly inhibited. When ECL cells were incubated with these proinflammatory cytokines, CINC-2 beta dose-dependently increased Reg messenger RNA and Reg protein in ECL cells. CXCR-2 was identified in isolated ECL cells.


CONCLUSIONS
CINC-2 beta, expressed in damaged gastric mucosa, stimulates the production of Reg protein in ECL cells via CXCR-2 and may be involved in the accelerated healing of injured gastric mucosa.
Kazumori
H
H
Second Department of Internal Medicine, Shimane Medical University, Izumo, Japan.
Ishihara
S
S
Hoshino
E
E
Kawashima
K
K
Moriyama
N
N
Suetsugu
H
H
Sato
H
H
Adachi
K
K
Fukuda
R
R
Watanabe
M
M
Takasawa
S
S
Okamoto
H
H
Fukui
H
H
Chiba
T
T
Kinoshita
Y
Y
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D002135:Calcium-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D019743:Chemokines, CXC; D002630:Chemotactic Factors / Q000276:immunology / Q000502:physiology*; D016207:Cytokines / Q000502:physiology; D004759:Enterochromaffin Cells / Q000378:metabolism / Q000502:physiology; D005753:Gastric Mucosa / Q000503:physiopathology*; D005755:Gastrins / Q000097:blood; D015870:Gene Expression / Q000187:drug effects / Q000502:physiology*; D006133:Growth Substances / Q000276:immunology / Q000502:physiology*; D007101:Immersion; D018836:Inflammation Mediators / Q000502:physiology; D036341:Intercellular Signaling Peptides and Proteins; D007375:Interleukin-1 / Q000235:genetics; D051847:Lithostathine; D008297:Male; D009419:Nerve Tissue Proteins; D009994:Osmolar Concentration; D051381:Rats; D017208:Rats, Wistar; D012149:Restraint, Physical; D013276:Stomach Ulcer / Q000097:blood / Q000209:etiology / Q000235:genetics / Q000503:physiopathology*; D013312:Stress, Physiological / Q000150:complications / Q000209:etiology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
D000906:Antibodies; D002135:Calcium-Binding Proteins; D019743:Chemokines, CXC; D002630:Chemotactic Factors; C513294:Cxcl3 protein, rat; D016207:Cytokines; D005755:Gastrins; D006133:Growth Substances; D018836:Inflammation Mediators; D036341:Intercellular Signaling Peptides and Proteins; D007375:Interleukin-1; D051847:Lithostathine; D009419:Nerve Tissue Proteins; C497616:Reg1a protein, rat; D014409:Tumor Necrosis Factor-alpha