Mechanism of Macrophage-Derived Chemokine/CCL22 Production by HaCaT Keratinocytes.

BACKGROUND: CC chemokine ligand 17 (CCL17) and CCL22 are the functional ligands for CCR4. We previously reported that inhibitors of nuclear factor-kappa B and p38 mitogen-activated protein kinase (p38 MAPK), but not of extracellular signal-related kinase (ERK), inhibited tumor necrosis factor (TNF)-α- and interferon (IFN)-γ-induced production of CCL17 by the human keratinocyte cell line, HaCaT. Further, an inhibitor of epidermal growth factor receptor (EGFR) enhanced the CCL17 production by these keratinocytes. OBJECTIVE: To identify the mechanism underlying CCL22 production by HaCaT cells. METHODS: We investigated the signal transduction pathways by which TNF-α and IFN-γ stimulate HaCaT cells to produce CCL22 by adding various inhibitors. RESULTS: TNF-α- and IFN-γ-induced CCL22 production was inhibited by PD98059, PD153035, Bay 11-7085, SB202190, c-Jun N-terminal kinase (JNK) inhibitor II, and Janus kinase (JAK) inhibitor 1. CONCLUSION: Our results indicate that CCL22 production in HaCaT cells is dependent on ERK, EGFR, p38 MAPK, JNK, and JAK and is mediated by different signal pathways from those regulating CCL17 production. Altogether, our previous and present results suggest that EGFR activation represses CCL17 but enhances CCL22 production by these cells.

Impact of disease severity on work productivity and activity impairment in Japanese patients with atopic dermatitis.

Atopic dermatitis (AD) is a common inflammatory skin disease that is characterized by chronic and persisting pruritic and eczematous lesions. There has been no study of work productivity and activity in AD patients in relation to disease severity. The purpose of this study was to examine the impact of disease severity on work productivity and activity impairment (WPAI) in adult AD patients using the Japanese version of the questionnaire. Data were collected from 112 AD patients who visited the Jikei University Hospital. Outcomes as measured by the questionnaire included employment status, total work productivity impairment (TWPI) and total activity impairment (TAI). We investigated the correlation between TWPI or TAI scores and severity scoring of AD (SCORAD) for disease severity and dermatology life quality index (DLQI) for quality of life impairment. Both TWPI and TAI scores were significantly correlated with the SCORAD and DLQI scores (P < 0.001), indicating disease severity is significantly associated with WPAI in Japanese adult AD patients. Further studies are necessary to evaluate the effects of treatments on WPAI for severe AD patients.

A case of angioedema associated with decreased C1 inhibitor activity.

BACKGROUND: We report a case of a 31-year-old woman who began to notice swelling of her arms at age 20. She was once given a diagnosis of cellulitis, but her symptoms spontaneously resolved. The patient had swelling of the left forearm and palm and was referred to our department for evaluation. She had slight pain but no obvious weight gain. CASE SUMMARY: Antinuclear antibody and other autoantibodies, including anti-ds-DNA antibody, anti-RNP antibody, anti-Sm antibody, and anti-SS-A antibody were not detected. C1 inhibitor activity was low, C3 was normal, C4 was low, CH(50) was low, and C1q was normal. DISCUSSION: Based on the presence of the typical clinical features and the positive results on the complement tests, we diagnosed hereditary angioedema. A decrease in C1 inhibitor activity and an increase in specific protein concentrations indicated type 1.