Abstract
To better clarify individual roles of interferon (IFN)-α and IFNγ in β-cell pathology during the onset of type 1 diabetes mellitus, we compared the effects of these cytokines on insulin production and major histocompatibility complex (MHC) gene expression in pancreatic β-cell lines. IFN-γ but not IFN-α decreased secreted and intracellular insulin concentrations in βTC6-F7 and βTC3 cells. Likewise, IFN-γ but not IFN-α treatment of β-cells upregulated mRNA expression of MHC class I(A) antigen- processing genes and surface expression of class I(A) molecules. Alternatively, class I(A) MHC expression was upregulated by IFN-γ and IFN- α in the P388D1 macrophage cell line. The observation of constitutive Ifn- α6 mRNA expression by a differentiated β-cell line substantiates previous indications that local expression of IFN-α in islets may trigger insulitis. Evidence that IFN-γ, a product of infiltrating leukocytes, directly decreases β-cell glucose sensitivity and increases MHC class I(A) cell surface expression supports the postulate that IFN-γ magnifies the insulitic process.
| Original language | English (US) |
|---|---|
| Pages (from-to) | C25-C32 |
| Journal | American Journal of Physiology - Cell Physiology |
| Volume | 275 |
| Issue number | 1 44-1 |
| State | Published - Jul 1 1998 |
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Keywords
- Insulitis
- Major histocompatibility complex class I(A) locus
- Type I diabetes
ASJC Scopus subject areas
- Physiology
- Cell Biology
Cite this
Interferon-α and interferon-γ differentially affect pancreatic β- cell phenotype and function. / Baldeón, Manuel E.; Chun, Taehoon; Gaskins, H. Rex.
In: American Journal of Physiology - Cell Physiology, Vol. 275, No. 1 44-1, 01.07.1998, p. C25-C32.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Interferon-α and interferon-γ differentially affect pancreatic β- cell phenotype and function
AU - Baldeón, Manuel E.
AU - Chun, Taehoon
AU - Gaskins, H. Rex
PY - 1998/7/1
Y1 - 1998/7/1
N2 - To better clarify individual roles of interferon (IFN)-α and IFNγ in β-cell pathology during the onset of type 1 diabetes mellitus, we compared the effects of these cytokines on insulin production and major histocompatibility complex (MHC) gene expression in pancreatic β-cell lines. IFN-γ but not IFN-α decreased secreted and intracellular insulin concentrations in βTC6-F7 and βTC3 cells. Likewise, IFN-γ but not IFN-α treatment of β-cells upregulated mRNA expression of MHC class I(A) antigen- processing genes and surface expression of class I(A) molecules. Alternatively, class I(A) MHC expression was upregulated by IFN-γ and IFN- α in the P388D1 macrophage cell line. The observation of constitutive Ifn- α6 mRNA expression by a differentiated β-cell line substantiates previous indications that local expression of IFN-α in islets may trigger insulitis. Evidence that IFN-γ, a product of infiltrating leukocytes, directly decreases β-cell glucose sensitivity and increases MHC class I(A) cell surface expression supports the postulate that IFN-γ magnifies the insulitic process.
AB - To better clarify individual roles of interferon (IFN)-α and IFNγ in β-cell pathology during the onset of type 1 diabetes mellitus, we compared the effects of these cytokines on insulin production and major histocompatibility complex (MHC) gene expression in pancreatic β-cell lines. IFN-γ but not IFN-α decreased secreted and intracellular insulin concentrations in βTC6-F7 and βTC3 cells. Likewise, IFN-γ but not IFN-α treatment of β-cells upregulated mRNA expression of MHC class I(A) antigen- processing genes and surface expression of class I(A) molecules. Alternatively, class I(A) MHC expression was upregulated by IFN-γ and IFN- α in the P388D1 macrophage cell line. The observation of constitutive Ifn- α6 mRNA expression by a differentiated β-cell line substantiates previous indications that local expression of IFN-α in islets may trigger insulitis. Evidence that IFN-γ, a product of infiltrating leukocytes, directly decreases β-cell glucose sensitivity and increases MHC class I(A) cell surface expression supports the postulate that IFN-γ magnifies the insulitic process.
KW - Insulitis
KW - Major histocompatibility complex class I(A) locus
KW - Type I diabetes
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M3 - Article
C2 - 9688831
AN - SCOPUS:0031827757
VL - 275
SP - C25-C32
JO - American Journal of Physiology - Cell Physiology
JF - American Journal of Physiology - Cell Physiology
SN - 0363-6143
IS - 1 44-1
ER -