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Nocardia fractions, NLD and NWSM, induce tumor necrosis factor-α secretion in human monocytes: Role of protein kinase C

✍ Scribed by Jean Louis Mege; Thiery Jacob; Pierre Bongrand; Christian Capo; Evguenine B. Myssiakine; Rita Barot-Ciorbaru

Publisher
John Wiley and Sons
Year
1993
Tongue
English
Weight
602 KB
Volume
23
Category
Article
ISSN
0014-2980

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✦ Synopsis

Abstract

Nocardia lysozyme digest (NLD) and Nocardia water‐soluble mitogen (NWSM) are two fractions derived from Nocardia opaca. In this report, we demonstrated that both fractions elicited significant secretion of tumor necrosis factor‐α (TNF‐α) in human monocytes. Supernatants from monocytes stimulated with NWSM and low concentrations of NLD displayed a cytotoxic activity against TNF‐α‐sensitive L929 cells, but supernatants from monocytes stimulated with high concentrations of NLD failed to lyse L929 cells. This latter phenomenon might be related to the secretion of an inactive form of TNF‐α or the release of an inhibitor of TNF‐α cytotoxic activity. Since it is well established that protein kinase C (PKC) plays a major role in the signaling of several monocyte activators, we investigated the putative role of PKC in cytokine synthesis induced by NLD and NWSM fractions. TNF‐α secretion in response to both Nocardia fractions was inhibited by sphingosine, staurosporine and calphostin C, known PKC inhibitors, as well as by a PKC depletion procedure. In addition, NLD and NWSM induced a transient increase in [^3^H] phorbol dibutyrate binding, which assessed the activation of PKC. The data suggest the involvement of PKC in the signaling of NLD and NWSM fractions leading to the synthesis and the secretion of TNF‐α by human monocytes.

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