Expression of mitogen activated protein kinases in labial salivary glands of patients with Sjögren's syndrome

Abstract

Objective: The expression of CD40 and CD40 ligand (CD40L) in mononuclear cells (MNCs) infiltrating the salivary glands of patients with Sjögren's syndrome (SS) has recently been reported. This study determined the expression of mitogen activated protein kinase (MAP kinase) superfamilies, which act as downstream effector molecules of CD40, in MNCs infiltrating labial salivary tissues in SS patients.

Methods: Six HTLV-I seronegative SS patients and 10 HTLV-I seropositive patients including five HTLV-I associated myelopathy (HAM) patients were examined. The expression of MAP kinase superfamilies in labial salivary glands was examined by immunohistochemistry containing the mirror section technique.

Results: Both active forms of c-Jun N-terminal kinase (JNK) and p38 were found in salivary infiltrating MNCs of SS patients. Only minimal expression of the active form of extracellular signal regulated kinase (ERK) was observed in these tissues, however, co-expression of active JNK and active p38 was confirmed by the mirror section technique. Furthermore, these protein kinases were co-expressed in CD40(+) MNCs. No difference in expression levels of active JNK and p38 was found in patients who were positive or negative for anti-HTLV-I antibody.

Conclusion: These results indicate that JNK and p38, but not ERK, function as downstream effector molecules of CD40 in salivary infiltrating MNCs in SS patients, and suggest that these molecules may be involved in the pathological process of chronic sialadenitis in SS.

Figure 1

Representative immunohistochemical analysis of JNK, p38 and ERK expression in serial sections of labial salivary glands from HTLV-I seropositive and seronegative SS patients. (A), (D), (G): HTLV-I seropositive SS patient. (B), (E), (H): HTLV-I seronegative SS patient. (C), (F), (I): Normal control (patient who have sicca symptoms but cannot to be diagnosed as SS by the European Community). (A), (B), (C): active form of JNK expression. (D), (E), (F): active form of p38 expression. (G), (H), (I): active form of ERK expression. (J): Rheumatoid arthritis synovium (positive control for ERK expression in synovial cells; arrowhead). Note that both active forms of JNK and p38 were found in SS patients with or without anti-HTLV-I antibody, however, neither JNK nor p38 was found in normal control. Little active form of ERK was detected in labial salivary glands. (Original magnification × 400).

Figure 2

Co-expression of JNK-p38, CD40-JNK, and CD40-p38 in mirror sections of labial salivary glands from HTLV-I-seropositive SS patients. (A), (B): active form of JNK (A) and p38 (B) were co-expressed in mirror sections in infiltrating MNCs (arrowhead). (C), (D): Co-expression of CD40 (C) and active form of JNK (D) in infiltrating MNCs (arrowhead). (E), (F): Co-expression of CD40 (E) and active form of p38 (F) in infiltrating MNCs (arrowhead). (Original magnification × 400).