Monoclonal Nonspecific Suppressor Factor β (MNSFβ) Inhibits the Production of TNF-α by Lipopolysaccharide-Activated Macrophages

Abstract The monoclonal nonspecific suppressor factor (MNSF), a lymphokine produced by a murine T cell hybridoma, shows a pleiotropic antigen-nonspecific suppressive function. Most recently, a cDNA encoding a subunit of MNSF (MNSFβ) has been isolated and characterized. Recombinant form of MNSFβ (rMNSFβ) inhibits lymphokine functions, as does native MNSF. In this study, we investigated whether rMNSFβ also affects macrophage function in terms of LPS-induced TNF-α production by a mouse macrophage cell line, J774. rMNSFβ suppressed the TNF-α production in a dose-dependent manner. This suppressive effect was remarkably reduced when rMNSFβ was added after 6 h of LPS stimulation. In addition, enhancement of TNF-α production by IFN-γ was also suppressed by rMNSFβ. The suppressive effect was partly neutralized by the addition of the serine/threonine phosphatase inhibitor, okadaic acid. This finding suggests that serine/threonine protein phosphatases type 1 and/or 2A may be implicated in the mechanism of action of MNSF.