T Shimizu1, R Abe, A Ohkawara, J Nishihira. 1. Department of Dermatology and the Central Research Institute, Hokkaido University School of Medicine, Sapporo, Japan.
Abstract
BACKGROUND: Atopic dermatitis (AD) is a chronic pruritic inflammatory skin disorder. The underlying cause of AD is multifactorial, and several cytokines are considered to be involved in this severe inflammatory skin disease. Macrophage migration inhibitory factor (MIF) is an immunoregulatory cytokine essential for T-cell activation and delayed-type hypersensitivity. Recently we demonstrated that serum MIF content was significantly elevated in patients with AD. Consistent with this, expression of MIF messenger RNA in keratinocytes of the eczematous skin lesion was up-regulated. OBJECTIVE AND METHOD: Although keratinocytes are considered to be a potential source of increased serum MIF content in AD, precise evaluation has not been carried out in other tissues. MIF is ubiquitously expressed in various cells, including T cells and macrophages. In this study we examined MIF production and its messenger RNA level of PBMCs from patients with AD to investigate the contribution of these cells to elevated serum MIF content and to its pathologic characteristics. RESULTS: Consistent with our previous findings, the serum MIF content of patients with AD was significantly elevated compared with nonatopic healthy control subjects and patients with chronic urticaria without eczema. As for the MIF productivity of unstimulated PBMCs, the MIF content in the culture medium of PBMCs obtained from patients with AD (40.4 +/- 8.4 ng/mL) (mean +/- SEM) was significantly increased compared with that from healthy control subjects (6.6 +/- 1.1 ng/mL) and patients with chronic urticaria (8.5 +/- 1.4 ng/ml) (P <.0001). When PBMCs were stimulated by concanavalin A, MIF production by PBMCs of patients with AD was more enhanced than in control subjects or patients with chronic urticaria. The increased ratio of MIF production by PBMCs in response to concanavalin A was significantly correlated with the severity of clinical features of AD. Supporting these results, the level of MIF mRNA in PMBCs of patients with AD was significantly higher than in nonatopic healthy control subjects. CONCLUSIONS: The current results showed that PBMCs should be an important source of increased serum MIF in AD. Because MIF has the potential to induce local and systemic inflammatory and immune responses, it is conceivable that MIF produced by PBMCs may affect local and systemic pathologic features in AD.
BACKGROUND:Atopic dermatitis (AD) is a chronic pruritic inflammatory skin disorder. The underlying cause of AD is multifactorial, and several cytokines are considered to be involved in this severe inflammatory skin disease. Macrophage migration inhibitory factor (MIF) is an immunoregulatory cytokine essential for T-cell activation and delayed-type hypersensitivity. Recently we demonstrated that serum MIF content was significantly elevated in patients with AD. Consistent with this, expression of MIF messenger RNA in keratinocytes of the eczematous skin lesion was up-regulated. OBJECTIVE AND METHOD: Although keratinocytes are considered to be a potential source of increased serum MIF content in AD, precise evaluation has not been carried out in other tissues. MIF is ubiquitously expressed in various cells, including T cells and macrophages. In this study we examined MIF production and its messenger RNA level of PBMCs from patients with AD to investigate the contribution of these cells to elevated serum MIF content and to its pathologic characteristics. RESULTS: Consistent with our previous findings, the serum MIF content of patients with AD was significantly elevated compared with nonatopic healthy control subjects and patients with chronic urticaria without eczema. As for the MIF productivity of unstimulated PBMCs, the MIF content in the culture medium of PBMCs obtained from patients with AD (40.4 +/- 8.4 ng/mL) (mean +/- SEM) was significantly increased compared with that from healthy control subjects (6.6 +/- 1.1 ng/mL) and patients with chronic urticaria (8.5 +/- 1.4 ng/ml) (P <.0001). When PBMCs were stimulated by concanavalin A, MIF production by PBMCs of patients with AD was more enhanced than in control subjects or patients with chronic urticaria. The increased ratio of MIF production by PBMCs in response to concanavalin A was significantly correlated with the severity of clinical features of AD. Supporting these results, the level of MIF mRNA in PMBCs of patients with AD was significantly higher than in nonatopic healthy control subjects. CONCLUSIONS: The current results showed that PBMCs should be an important source of increased serum MIF in AD. Because MIF has the potential to induce local and systemic inflammatory and immune responses, it is conceivable that MIF produced by PBMCs may affect local and systemic pathologic features in AD.
Authors: Rituparna Das; Jeremy E Moss; Eve Robinson; Scott Roberts; Rebecca Levy; Yuka Mizue; Lin Leng; Courtney McDonald; Robert E Tigelaar; Christina A Herrick; Richard Bucala Journal: J Clin Immunol Date: 2011-05-11 Impact factor: 8.317