Hyaluronectin secretion by monocytes: Downregulation by IL-4 and IL-13, upregulation by IL-10

Hyaluronectin (HN) is a component of the extracellular matrix of connective tissue and is particularly associated with tumour inflammatory and connect ive stroma reaction, where it co-localizes with hyaluronic acid (HA), The H N/HA ratio has been suggested to be involved in tumour aggressivity and in the atherosclerosis process. IL-10 has also been described in atherosclerot ic lesions and in cancer. HN production was therefore investigated in vitro in peripheral blood monocyte cell (PBMC) cultures, with and without bacter ial lipolysaccharide (LPS) or interleukins (ILs) in the medium. HN was char acterized in monocytic cell cytoplasm and in culture supernatants. Anti-IL- 10 antibody suppressed the LPS-stimulating effect on HN production. HN synt hesis rate was greatly increased in IL-10-activated cultures while IL-4 and IL-13, two other anti-inflammatory ILs, decreased HN release. In the prese nce of IL-10, the IL-4 or II-13 inhibitory effect on HN synthesis was rever sed. The results support the view that intratumoral release of IL-10 by mon ocytes may induce local production of HN, In conjunction with the known abi lity of HN to bind to HA, which is a cell migration and tumour invasion fac ilitating factor, and to inhibit HA-induced angiogenesis, our findings sugg est that HN may modulate the effect of HA on atherosclerosis, angiogenesis and cancer development. (C) 1999 Academic Press.