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Lorise C. Gahring

Professor of Medicine and of Pathology

B.A. University of California, Irvine

Ph.D. University of Utah

Research

References

lorise.gahring@hsc.utah.edu

Lorise Gahring's PubMed Literature Search

Research

Inflammation plays a pivotal role in disease processes of both the peripheral immunologic system and in the central nervous system (CNS). Many of the early inflammatory events in these tissues are regulated through the production of cytokines and chemokines.  A receptor system that influences the production of inflammatory cytokines/chemokines is the nicotinic acetylcholine receptor (nAChR) which are ligand gated ion channels expressed by many different cell types ranging from immune cells  to neurons.  Endogenous ligands for the nAChR include acetylcholine and choline which modulate neurotransmission and development of the nervous system. An exogenous ligand is nicotine and thus addictive behaviors are modulated through this receptor system.  In both peripheral and central systems the activation of one nAChR subtype, alpha7 (a7), results in alterations in cytokine production.  We know this through the use of a7 knock-out mice which demonstrate elevated levels of pro-inflammatory cytokines during an inflammatory event.  It has been difficult to accurately assess the cell types responsible for these alterations in cytokine production due to the low levels of receptor expression. Therefore, we have generated an a7cre expressing mouse that upon crossing with ROSA-YFP mice results in animals which are lineage marked with a7-YFP.  Peripheral and central cells from these animals can be characterized by flow cytometry, and sorted via FACS to determine the specific cell type influenced by this nicotinic receptor.  Macrophages, major regulatory cells of inflammatory processes in both the CNS and peripheral immune system, express a7.

We are now addressing whether there is a specific macrophage phenotype associated with the expression of nAChRa7 and what cytokines/chemokines are affected by receptor activation. The importance of this question lies in the now described subsets of macrophages known as ‘classically activated, M1-type pro-inflammatory macrophages’ or ‘alternatively activated, M2-type macrophages’ that are more anti-inflammatory.  Differential activities of these macrophage subtypes influence the response to infectious disease as well as tumor progression.   We are also addressing the questions of how the endogenous ligands such as choline (a dietary supplement) and acetylcholine as well as exogenous ligands such as nicotine influence the development of the peripheral immune system which ultimately influences adult functions.   

 

References