Immunomodulated
Signaling in Macrophages:Regulation of the MAPK Signaling Pathways by PKA and
PKC
LIN Min-Qun and CHANG Zong-Liang
( Shanghai Institute of cell Biochemistry， Chinese Academy of Sciences，Shanghai 200031，China )
Abstract Previous
experimental investigation indicated that immuno-suppressor activities of
suppressor macrophages on T，B lymphocytes and NK cells could be
prevented by treatment with LPS，but the tumoricidal activities of those
macrophages could be kept or even enhanced after the same treatment.During this
complicated course，LPS-mediated immuno-modulation was
accompanied by activation of PKC and MAPK signal pathways.In order to explore
the effect of another signal on MAPK pathway ，this model of immuno-modulated
macrophage was utilized to study the regulatory effect on the activation of
three family members of MAPK (ERK1/2，JNK and p38) by cAMP/PKA and
PMA/PKC.The results showed that 1) LPS-mediated immuno-modulation was
accompanied by dynamic changes of intracellular cAMP amount and PKA activity.
2) A specific PKC activator，PMA，induced strongly the
activation of ERK1/2，JNK and p38 MAPK. 3) In contrast，the activation of cAMP/PKA
mediated a significant inhibiton of the phosphorylation of ERK1/2，JNK and p38 MAPK and ATF-2，but it enhanced the
phosphorylation of CREB.These results suggest that a complicated“cross-talk”may
exist among PKC and PKA and MAPK signaling pathways in the regulation of murine
peritoneal suppressor macrophages by LPS.
Key Words macrophage LPS-mediated immune
modulation；PKA；PKC；MAPK；CREB/ATF-2
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