D-pinitol inhibits Th1 polarization via the suppression of dendritic cells.
d-pinitol has been demonstrated to exert insulin-like and anti-inflammatory effects. However, the effects of the maturation and immunostimulatory functions of dendritic cells (DC) remain to be clearly elucidated. In this study, we have attempted to determine whether d-pinitol regulates surface molecule expression, cytokine production, endocytosis capacity, and underlying signaling pathways in murine bone marrow-derived DC. We also attempted to ascertain whether d-pinitol could influence Th1/Th2 immune response in vivo. The DC used in this study were derived from murine bone marrow cells, and were used as immature or LPS-stimulated mature DC. The DC were then assessed with regard to surface molecule expression, dextran-FITC uptake, cytokine production, capacity to induce T-cell differentiation, and underlying signaling pathways. d-pinitol was shown to significantly inhibit CD80, CD86, MHC class I, and MHC class II expression in the LPS-stimulated mature DC. The DC also evidenced impaired IL-12 expression and IFN-gamma production. The d-pinitol-treated DC were found to be highly efficient in regards to Ag capture via mannose receptor-mediated endocytosis. d-pinitol was also demonstrated to inhibit LPS-induced MAPKs activation and NF-kappaB nuclear translocation. Moreover, the d-pinitol-treated DC manifested impaired induction of Th1 responses, and normal cell-mediated immune responses. These novel findings provide new insight into the immunopharmacological role of d-pinitol in terms of its effects on DC. These findings also broaden current perspectives concerning our understanding of the immunopharmacological functions of d-pinitol, and have ramifications for the development of therapeutic adjuvants for the treatment of DC-related acute and chronic diseases.
Lee
Jun Sik
JS
Department of Pharmacy, Pusan National University College of Pharmacy, Busan, South Korea.
Jung
In Duk
ID
Jeong
Young-Il
YI
Lee
Chang-Min
CM
Shin
Yong Kyoo
YK
Lee
Sang-Yull
SY
Suh
Dong-Soo
DS
Yoon
Man-Soo
MS
Lee
Kyu-Sub
KS
Choi
Yung Hyun
YH
Chung
Hae Young
HY
Park
Yeong-Min
YM
D000818:Animals; D015703:Antigens, CD / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D007155:Immunologic Factors / Q000494:pharmacology*; D007294:Inositol / Q000031:analogs & derivatives* / Q000494:pharmacology; D007371:Interferon-gamma / Q000276:immunology; D018664:Interleukin-12 / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D020928:Mitogen-Activated Protein Kinases / Q000276:immunology
D015703:Antigens, CD; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D007155:Immunologic Factors; D018664:Interleukin-12; C021730:pinitol; D007294:Inositol; D007371:Interferon-gamma; D020928:Mitogen-Activated Protein Kinases