Background: High mobility group box-1 (HMGB1) is a ubiquitously expressed non-histone nuclear protein which acts as a danger signal when released from cells. HMGB1, which is associated with inflammation, angiogenesis, and T helper (Th)2 polarization, contributes to the development of various inflammatory diseases and malignancies. However, it remains to be determined whether HMGB1 is involved in cutaneous T-cell lymphoma (CTCL).
Objectives: To investigate the role of HMGB1 in CTCL.
Materials & methods: Serum HMGB1 levels were measured in patients with CTCL and healthy controls using an enzyme-linked immunosorbent assay. HMGB1 messenger RNA (mRNA) expression in CTCL and normal skin was examined by quantitative reverse transcription polymerase chain reaction and immunohistochemistry. Moreover, we analysed correlations between the levels of HMGB1 and other cytokines and chemokines, laboratory data, disease activity, and prognosis.
Results: HMGB1 levels were significantly higher in sera of CTCL patients than those of normal controls and correlated with serum levels of soluble interleukin-2 receptor, lactate dehydrogenase, thymus and activation-regulated chemokine, and the number of eosinophils in peripheral blood. Serum HMGB1 levels also reflected disease activity and prognosis for each patient with CTCL. HMGB1 mRNA levels in CTCL lesional skin were significantly elevated and correlated with IL-4, IL-10, IL-19, and angiogenin mRNA levels. Immunohistochemical staining revealed that HMGB1 was expressed not only in the nucleus but also in the cytoplasm of various cells in CTCL lesional skin.
Conclusion: These results suggest that enhanced HMGB1 expression may contribute to the progression of CTCL through Th2 polarization and promotion of angiogenesis.
Keywords: HMGB1; Th2 polarization; angiogenesis; cutaneous T-cell lymphoma; mycosis fungoides.