Ds. Adams et al., Activation of a rel-A/CEBP-beta-related transcription factor heteromer by PGG-glucan in a murine monocytic cell line, J CELL BIOC, 77(2), 2000, pp. 221-233
PGG-Glucan is a soluble beta-glucan immunomodulator that enhances a variety
of leukocyte microbicidal activities without activating inflammatory cytok
ines. Although several different cell surface receptors for soluble (and pa
rticulate) beta-glucans have been described, the signal transduction pathwa
y(s) used by these soluble ligands have not been elucidated. Previously we
reported that PGG-Glucan treatment of mouse BMC2.3 macrophage cells activat
es a nuclear factor kappa-B-like (NF-kappa 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 enhanc
er-binding protein-beta (C/EBP-beta)-related molecule with an apparent size
of 48 kDa, which is a different protein than the previously identified C/E
BP-beta p34 also present in these cells. C/EBP-beta is a member of the bZIP
family whose members have previously been shown to interact with rel famil
y members. This rel/bZIP heteromer complex activated by PGG-Glucan is diffe
rent from the p65/p50 rel/rel complex induced in these cells by lipopolysac
charide (LPS). Thus, our data demonstrate that PGG-Glucan uses signal trans
duction pathways different from those used by LPS, which activates leukocyt
e microbicidal activities and inflammatory cytokines. We further show that
heteromer activation appears to use protein kinase C (PKC) and protein tyro
sine kinase (PTK) pathways, but not mitogen-activated protein kinase p38. I
nhibitor K-B-a (IKB-alpha) is associated with the heteromer; this associati
on decreases after PGG-Glucan treatment. These data are consistent with a m
odel whereby treatment of BMC2.3 cells with PGG-Glucan activates I kappa B-
alpha via PKC and/or PTK pathways, permitting translocation of the rel-A/CE
BP-beta heteromer complex to the nucleus and increases its DNA-binding affi
nity. J. Cell. Biochem. 77:221-233, 2000. (C) 2000 Wiley-Liss, Inc.