Involvement of the interferon-gamma-induced T cell-attracting chemokines, interferon-gamma-inducible 10-kd protein (CXCL10) and monokine induced by interferon-gamma (CXCL9), in the salivary gland lesions of patients with Sjögren's syndrome.
OBJECTIVE
To elucidate the mechanism of the development of T cell infiltrates in the salivary glands of patients with Sjögren's syndrome (SS), we studied T cell-attracting chemokines and their receptors.


METHODS
The expression of the T cell-attracting chemokines, interferon-gamma (IFNgamma)-inducible 10-kd protein (IP-10; also called CXCL10), monokine induced by IFNgamma (Mig; also called CXCL9), and stromal cell-derived factor 1 (SDF-1; also called CXCL12), in salivary glands from SS patients was investigated by polymerase chain reaction-enzyme-linked immunosorbent assay (ELISA). Cells that produce chemokines and lymphocytes that express chemokine receptors were identified by immunohistochemistry. The production of IP-10 and Mig proteins by salivary epithelial cells in response to IFNgamma was determined by ELISA.


RESULTS
Expression of IP-10 and Mig messenger RNA (mRNA) was significantly up-regulated in SS salivary glands compared with normal salivary glands (both P < 0.01). There was no significant difference in SDF-1 mRNA expression between the SS and normal salivary glands. IP-10 and Mig proteins were predominantly expressed in the ductal epithelium adjacent to lymphoid infiltrates. Most of the CD3+ infiltrating lymphocytes in dense periductal foci expressed CXCR3, the receptor for IP-10 and Mig. IFNgamma induced the production of high levels of IP-10 and Mig proteins from cultured SS salivary epithelial cells.


CONCLUSIONS
These findings suggest that IFNgamma stimulates the production of IP-10 and Mig in the SS ductal epithelium, and that IP-10 and Mig are involved in the accumulation of T cell infiltrates in the SS salivary gland. Chemokines or chemokine receptors could be a rational new therapeutic target in SS.
Ogawa
Noriyoshi
N
Division of Hematology and Immunology, Department of Internal Medicine, Kanazawa Medical University, 1-1 Daigaku, Uchinada-machi, Kahoku-gun, Ishikawa-ken 920-0293, Japan. nogawa@kanazawa-med.ac.jp
Ping
Li
L
Zhenjun
Li
L
Takada
Yukiko
Y
Sugai
Susumu
S
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002478:Cells, Cultured; D054357:Chemokine CXCL10; D054370:Chemokine CXCL9; D019743:Chemokines, CXC / Q000235:genetics*; D004847:Epithelial Cells / Q000187:drug effects / Q000276:immunology; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D007371:Interferon-gamma / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000032:analysis; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine / Q000235:genetics; D018987:Salivary Ducts / Q000166:cytology / Q000276:immunology; D012469:Salivary Glands / Q000166:cytology / Q000276:immunology*; D012859:Sjogren's Syndrome / Q000276:immunology*; D013601:T-Lymphocytes / Q000502:physiology*
C080810:CXCL9 protein, human; C515187:CXCR3 protein, human; D054357:Chemokine CXCL10; D054370:Chemokine CXCL9; D019743:Chemokines, CXC; D036341:Intercellular Signaling Peptides and Proteins; D012333:RNA, Messenger; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine; D007371:Interferon-gamma