Involvement of protein kinases in signalling for nitric oxide (NO) and tumour necrosis factor alpha (TNF) production by monocytes stimulated with colorectal DeTa cancer cells: the lack of evidence for the role of TNF in the regulation of NO production

Kinases that are involved in NO and TNF production by human monocytes (MO) stimulated by colorectal cancer (DeTa) cells and effects of exogenous and e ndogenously synthesized TNF on NO induction were studied. The results based on the use of various inhibitors of protein kinases suggest that different signalling pathways operate in MO during induction of TNF and NO release a fter stimulation by DeTa cells. Stimulation of NO production required at le ast PTK, PKC and PKA, but only PTK and PKC were engaged in signal transduct ion for TNF production. Exogenous TNF and TNF produced by MO upon contact w ith DeTa cells was not sufficient for the induction or enhancement of NO sy nthesis in MO. The TNF synthesis was not influenced by neither exogenous no r endogenous NO produced by MO in the co-culture. Therefore, signal transdu ction pathways operating in MO during NO induction seem to be different fro m these engaged in TNF production, and both regulatory pathways probably op erate in MO independently. (C) 1999 Elsevier Science B.V. All rights reserv ed.