ABSTRACT
Melanocyte loss in vitiligo vulgaris is believed to be an autoimmune process. Macrophage migration inhibitory factor (MIF) is involved in many autoimmune skin diseases. We determined the possible role of MIF in the pathogenesis of vitiligo vulgaris, and describe the relationship between MIF expressions and disease severity and activity. Serum MIF concentrations and mRNA levels in PBMCs were measured in 44 vitiligo vulgaris patients and 32 normal controls, using ELISA and real-time RT-PCR. Skin biopsies from 15 patients and 6 controls were analyzed by real-time RT-PCR. Values are reported as median (25th-75th percentile). Serum MIF concentrations were significantly increased in patients [35.81 (10.98-43.66) ng/mL] compared to controls [7.69 (6.01-9.03) ng/mL]. MIF mRNA levels were significantly higher in PBMCs from patients [7.17 (3.59-8.87)] than controls [1.67 (1.23-2.42)]. There was also a significant difference in MIF mRNA levels in PBMCs between progressive and stable patients [7.86 (5.85-9.13) vs 4.33 (2.23-8.39)] and in serum MIF concentrations [40.47 (27.71-46.79) vs 26.80 (10.55-36.07) ng/mL]. In addition, the vitiligo area severity index scores of patients correlated positively with changes of both serum MIF concentrations (r = 0.488) and MIF mRNA levels in PBMCs (r = 0.426). MIF mRNA levels were significantly higher in lesional than in normal skin [2.43 (2.13-7.59) vs 1.18 (0.94-1.83)] and in patients in the progressive stage than in the stable stage [7.52 (2.43-8.84) vs 2.13 (1.98-2.64)]. These correlations suggest that MIF participates in the pathogenesis of vitiligo vulgaris and may be useful as an index of disease severity and activity.
Subject(s)
Adolescent , Adult , Female , Humans , Male , Middle Aged , Young Adult , Leukocytes, Mononuclear/chemistry , Macrophage Migration-Inhibitory Factors/metabolism , RNA, Messenger/metabolism , Vitiligo/metabolism , Case-Control Studies , Enzyme-Linked Immunospot Assay , Macrophage Migration-Inhibitory Factors/analysis , Reverse Transcriptase Polymerase Chain Reaction , Severity of Illness Index , Vitiligo/etiology , Vitiligo/pathologyABSTRACT
<p><b>OBJECTIVE</b>To study the influence of tumor-associated macrophages (TAMs) on the biological function of SW620 cell.</p><p><b>METHODS</b>Macrophage was induced into M2-type macrophage form with interleukin (IL)-4. CD68, macrophage mannose receptor (MMR), and inducible nitric oxide synthase (iNOS) were analyzed with Western blot. SW620 was co-cultured with TAMs in the Transwell. Cytokines including IL-10, IL-12, IL-23, and tramsforming growth factor-β (TGF-β) were detected with enzyme-linked immunosorbent assay (ELISA). The activity of nuclear factor-κB (NF-κB) in SW620 was analyzed with electrophoretic mobility shift assay (EMSA). The proliferation and apoptosis of SW620 cells after co-cultured with TAM were determined with tetrazolium four nitrogen (XTT) assay and fluorescence activated cell sorting (FACS), respectively. RESULTS IL-4 induced M2 type macrophage expressed CD68 and MMR instead of iNOS. After co-cultured with SW620 for 24 hours and 48 hours, M2 type macrophage secreted higher levels of IL-10 and TGF-β than the pre-culture level (P 0.05). The activity of NF-κB in SW620 decreased by 72% and 75% after 24 hours and 48 hours compared with the pre-culture level, respectively (both P<0.01). The activity of proliferation decreased by 48% and 59% and the apoptotic rates increased by 6.37% and 7.68% and 0.37% after 24 hours and 48 hours (all P<0.01) compared with the pre-culture levels.</p><p><b>CONCLUSION</b>TAM may inhibit the proliferation and promote the apoptosis of SW620 by suppressing the activity of NF-κB.</p>