AhR- and c-maf-dependent induction of β7-integrin expression in human macrophages in response to environmental polycyclic aromatic hydrocarbons
Section snippets
Experimental procedures
Chemicals and reagents. PAHs and α-naphthoflavone (αNF) were purchased from Sigma–Aldrich (St. Louis, MO). TCDD was obtained from Cambridge Isotope Laboratories (Cambridge, MA). Rabbit polyclonal Ab anti-AhR (SA-210) was obtained from Biomol Research Labs (Plymouth, PA) whereas rabbit non-specific IgG was from Amersham Biosciences (Orsay, France). Rabbit polyclonal Abs anti-c-maf (M-153) and anti-p38 MAPK and mouse monoclonal Ab anti-lamin A/C were purchased from Santa Cruz Biotechnology (Tebu,
PAH-triggered induction of β7 ITG expression
ITG family comprises eighteen α and eight β subunits which assemble to form at least 24 heterodimers (Fig. 1A), and whose mRNA levels in human primary macrophages exposed to 10 μM BP were first investigated by RT-qPCR (Fig. 1B). α11, αL, αE, β7, and β8 ITG mRNA levels were found to be significantly increased by the PAH whereas, by contrast, level of α9 ITG was decreased when compared to untreated macrophages (Fig. 1B). Other ITG subunits, constitutively expressed in untreated primary
Discussion
In the present report, we demonstrate that β7 ITG constitutes a robust molecular target of PAHs. Indeed, these environmental contaminants were shown to in vitro up-regulate β7 ITG in human macrophages at both mRNA and protein levels whereas in vivo PAH exposure enhanced β7 ITG expression in rat intestine. Such an up-regulation of β7 ITG by PAHs likely accounts for the induction of this ITG in response to diesel particles since such particles are well-known to contain PAHs [8].
AhR, well-known to
Acknowledgments
This work was supported by grants from Agence Française de Sécurité Sanitaire de l’Environnement et du Travail (AFSSET). Patricia Monteiro is a recipient of fellowship from the Ligue contre le Cancer. We thank Drs. D. Lagadic-Gossmann, A. Eychène, and M.P. Felder-Schmittbuhl for helpful discussions. We are grateful to Dr. L. Sparfel for in vivo experiments.
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