Suppression by ¦¤⁹-tetrahydrocannabinol of the primary immunoglobulin M response by human peripheral blood B cells is associated with impaired STAT3 activation

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• 作者：Thitirat Ngaotepprutaram ; Barbara L.F. Kaplan ; Stephen Carney ; Robert Crawford ; Norbert E. Kaminski
• 关键词：CD40L ; CD40 ligand ; CFSE ; carboxyfluorescein succinimidyl ester ; ¦¤9-THC¦¤ ; 9-tetrahydrocannabinol ; HPB ; human peripheral blood ; IgM ; immunoglobulin M ; ICAM ; intercellular adhesion molecule ; IL ; interleukin ; NA ; naï ; ve ; STAT ; signal transducer and act
• 刊名：Toxicology
• 出版年：2013
• 出版时间：9 August, 2013
• 年：2013
• 卷：310
• 期：Complete
• 页码：84-91
• 全文大小：1532 K

文摘

This study was undertaken to gain insights into the mechanism for ¦¤⁹-tetrahydrocannabinol (¦¤⁹-THC)-mediated suppression of primary immunoglobulin M (IgM) responses in humans. An in vitro activation model, which employs cell surface-expressed CD40 ligand (CD40L) and recombinant cytokines (interleukin (IL)-2, -6, and -10), was used to differentiate human peripheral blood (HPB) na?ve B cells into IgM secreting cells. Pretreatment with ¦¤⁹-THC significantly decreased the number of IgM secreting cells as determined by ELISPOT. The attenuation of IgM secretion by ¦¤⁹-THC involved, at least in part, the impairment of plasma cell differentiation as evidenced by suppression of immunoglobulin joining chain (IgJ) mRNA expression. The analysis at each of two different stages critically involved in plasma cell differentiation indicates that ¦¤⁹-THC impaired both the primary activation stage and proliferation of B cells. Interestingly, ¦¤⁹-THC selectively suppressed the surface expression of CD80, but not other measured B-cell activation markers (CD69, CD86, and ICAM1). Furthermore, pretreatment with ¦¤⁹-THC was accompanied by a robust decrease of STAT3 phosphorylation, whereas the phosphorylation of the p65 NF¦ÊB subunit was not affected. Collectively, these data provide new insights into the mechanisms for impaired B cell function by ¦¤⁹-THC.