Activation of a Rel-A/CEBP-β-related transcription factor heteromer by PGG-Glucan in a murine monocytic cell line
✍ Scribed by David S. Adams; Robin Nathans; Stephanie C. Pero; Ami Sen; Eric Wakshull
- Publisher
- John Wiley and Sons
- Year
- 2000
- Tongue
- English
- Weight
- 232 KB
- Volume
- 77
- Category
- Article
- ISSN
- 0730-2312
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✦ Synopsis
PGG-Glucan is a soluble -glucan immunomodulator that enhances a variety of leukocyte microbicidal activities without activating inflammatory cytokines. Although several different cell surface receptors for soluble (and particulate) -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 -B-like (NF-B) 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- (C/EBP-)-related molecule with an apparent size of 48 kDa, which is a different protein than the previously identified C/EBP- p34 also present in these cells. C/EBP- 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 microbicidal 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 -B-␣ (IB-␣) 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 IB-␣ via PKC and/or PTK pathways, permitting translocation of the rel-A/CEBP- heteromer complex to the nucleus and increases its DNAbinding affinity.