Activation of a Rel-A/CEBP-?-related transcription factor heteromer by PGG-Glucan in a murine monocytic cell line

Autor: Eric Wakshull, David S. Adams, Ami Sen, Stephanie C. Pero, Robin S. Nathans
Rok vydání: 2000
Předmět:
Zdroj: Journal of Cellular Biochemistry. 77:221-233
ISSN: 1097-4644
0730-2312
DOI: 10.1002/(sici)1097-4644(20000501)77:2<221::aid-jcb6>3.0.co;2-v
Popis: PGG-Glucan is a soluble b-glucan immunomodulator that enhances a variety of leukocyte microbi- cidal activities without activating inflammatory cytokines. Although several different cell surface receptors for soluble (and particulate) b-glucans have been described, the signal transduction pathway(s) used by these soluble ligands have not been elucidated. Previously we reported that PGG-Glucan treatment of mouse BMC2.3 macrophage cells activates a nuclear factor k-B-like (NF-kB) transcription factor complex containing subunit p65 (rel-A) attached to an unidentified cohort. In this study, we identify the cohort to be a non-rel family member: a CCAAT enhancer-binding protein-b (C/EBP-b)-related molecule with an apparent size of 48 kDa, which is a different protein than the previously identified C/EBP-b p34 also present in these cells. C/EBP-b is a member of the bZIP family whose members have previously been shown to interact with rel family members. This rel/bZIP heteromer complex activated by PGG-Glucan is different from the p65/p50 rel/rel complex induced in these cells by lipopolysaccharide (LPS). Thus, our data demonstrate that PGG-Glucan uses signal transduction pathways different from those used by LPS, which activates leukocyte microbi- cidal activities and inflammatory cytokines. We further show that heteromer activation appears to use protein kinase C (PKC) and protein tyrosine kinase (PTK) pathways, but not mitogen-activated protein kinase p38. Inhibitor k-B-a (IkB-a) is associated with the heteromer; this association decreases after PGG-Glucan treatment. These data are consistent with a model whereby treatment of BMC2.3 cells with PGG-Glucan activates IkB-a via PKC and/or PTK pathways, permitting translocation of the rel-A/CEBP-b heteromer complex to the nucleus and increases its DNA- binding affinity. J. Cell. Biochem. 77:221-233, 2000. © 2000 Wiley-Liss, Inc.
Databáze: OpenAIRE
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