Cytokine regulation of prolyl 4-hydroxylase production in skin fibroblast cultures from patients with systemic sclerosis: contribution to collagen synthesis and fibrosis.
Prolyl 4-hydroxylase (PH) is an enzyme that catalyzes an essential step in procollagen synthesis. PH production, as measured by the new ELISA method, was significantly higher in fibroblast cultures from patients with systemic sclerosis (SSc; N = 7) than in cultures from healthy controls (NC; N = 5) (p less than 0.01). Transforming growth factor-beta and tumor necrosis factor-alpha significantly increased PH production, but recombinant interferon-gamma had a significant negative effect on PH production. Since the production of PH is relevant to collagen synthesis by fibroblasts of patients with SSc, regulation of PH production may have therapeutic value.
Kawaguchi
Y
Y
First Department of Internal Medicine, National Defense Medical College, Saitama, Japan.
Kitani
A
A
Hara
M
M
Harigai
M
M
Hirose
T
T
Suzuki
K
K
Kawakami
M
M
Hidaka
T
T
Ishizuka
T
T
Kawagoe
M
M
D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism*; D016207:Cytokines / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay; D005347:Fibroblasts / Q000201:enzymology* / Q000473:pathology; D005355:Fibrosis / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D015151:Immunoblotting; D007371:Interferon-gamma / Q000494:pharmacology; D011347:Procollagen / Q000378:metabolism; D011393:Procollagen-Proline Dioxygenase / Q000378:metabolism*; D011863:Radioimmunoassay; D011994:Recombinant Proteins / Q000494:pharmacology; D012595:Scleroderma, Systemic / Q000201:enzymology* / Q000473:pathology / Q000503:physiopathology; D012867:Skin / Q000201:enzymology* / Q000473:pathology; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D016207:Cytokines; D011347:Procollagen; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D003094:Collagen; D011393:Procollagen-Proline Dioxygenase