Reciprocal Regulation of Chitinase 3-like1 Production from Human Macrophages by Th1 and Th2 Cytokines

Abstract

RATIONALE: Chitinase 3-like 1 (CHI3L1) is a mammalian member of chitinase family. The group of this family consists of catalytically active members (chitinase-1 and acid mammalian chitinase; AMCase) and several inactive ones (CHI3L1 and CHI3L2). AMCase is produced via a IL-13-dependent pathway and associated with the pathogenesis of chronic rhinosinusitis. CHI3L1 is evaluated in rheumatoid arthritis, osteoarthritis and scleroderma. Using microarray, we recently found that CHI3L1 is highly expressed in macrophages. Here we investigated the effect of cytokines on CHI3L1 expression by GM-CSF- or M-CSF induced macrophages.METHODS: Monocytes were obtained from PBMC of healthy volunteers and were cultured with GM-CSF or M-CSF for 7 days. During the culture, >98% of monocytes were differentiated into macrophages. The cells were incubated with Th1 or Th2 cell-derived cytokines for 48 hours. The supernatants were collected to examine the protein levels of CHI3L1 using ELISA. Human microvascular endothelial cells (HMVEC) were cultured in presence or absence of purified CHI3L1. Cell proliferation assay was performed by using BrdU.RESULTS: CHI3L1 was constitutively expressed by GM-CSF-induced macrophages. IFN-γ as well as IL-10 significantly up-regulated the production of CHI3L1, while IL-4 and IL-13 significantly suppressed it. Purified CHI3L1 significantly suppressed the cell proliferation on on HMVEC.CONCLUSIONS: CHI3L1 production by macrophages was up-regulated by IFN-γ and was suppressed by IL-4 and IL-13. These results suggest that the production of CHI3L1 by macrophages was reciprocally regulated by IFN-γ and IL-4, and CHI3L1 may play an inhibitory role in angiogenesis. RATIONALE: Chitinase 3-like 1 (CHI3L1) is a mammalian member of chitinase family. The group of this family consists of catalytically active members (chitinase-1 and acid mammalian chitinase; AMCase) and several inactive ones (CHI3L1 and CHI3L2). AMCase is produced via a IL-13-dependent pathway and associated with the pathogenesis of chronic rhinosinusitis. CHI3L1 is evaluated in rheumatoid arthritis, osteoarthritis and scleroderma. Using microarray, we recently found that CHI3L1 is highly expressed in macrophages. Here we investigated the effect of cytokines on CHI3L1 expression by GM-CSF- or M-CSF induced macrophages. METHODS: Monocytes were obtained from PBMC of healthy volunteers and were cultured with GM-CSF or M-CSF for 7 days. During the culture, >98% of monocytes were differentiated into macrophages. The cells were incubated with Th1 or Th2 cell-derived cytokines for 48 hours. The supernatants were collected to examine the protein levels of CHI3L1 using ELISA. Human microvascular endothelial cells (HMVEC) were cultured in presence or absence of purified CHI3L1. Cell proliferation assay was performed by using BrdU. RESULTS: CHI3L1 was constitutively expressed by GM-CSF-induced macrophages. IFN-γ as well as IL-10 significantly up-regulated the production of CHI3L1, while IL-4 and IL-13 significantly suppressed it. Purified CHI3L1 significantly suppressed the cell proliferation on on HMVEC. CONCLUSIONS: CHI3L1 production by macrophages was up-regulated by IFN-γ and was suppressed by IL-4 and IL-13. These results suggest that the production of CHI3L1 by macrophages was reciprocally regulated by IFN-γ and IL-4, and CHI3L1 may play an inhibitory role in angiogenesis.