Phosphorylated p38 MAP kinase expression by leucocytes is increased in allergic humans and associated with IgE responses

Authors

Jonathan I. Silverberg, Department of Dermatology, George Washington University School of Medicine and Health Sciences, Washington, District of Columbia, USA.
Tamar A. Smith-Norowitz, Department of Pediatrics, State University of New York Downstate Health Sciences University, Brooklyn, New York, USA.
Stephan Kohlhoff, Department of Pediatrics, State University of New York Downstate Health Sciences University, Brooklyn, New York, USA.
Rauno Joks, Department of Medicine, State University of New York Downstate Health Sciences University, Brooklyn, New York, USA.

Document Type

Journal Article

Publication Date

3-1-2024

Journal

Scandinavian journal of immunology

Volume

99

Issue

3

DOI

10.1111/sji.13343

Keywords

IgE; MAP kinase; allergic rhinoconjunctivitis; allergy; asthma; mitogen‐activated protein kinase; phosphorylated ERK1/2; phosphorylated JNK; phosphorylated p38

Abstract

Mitogen-activated protein kinases (MAPK) activate cascades that regulate cell proliferation, differentiation and death. Phosphorylated (phos-)p38 MAPK is a cell-signalling pathway associated with Th2 cytokine responses, which is required for immunoglobulin (Ig)E production. It is unknown whether MAPK are associated with IgE production. We examine the evidence linking p38 MAPK to inflammatory responses. Phos-p38, extracellular signal-related kinase (ERK) and c-JUN-n terminal (JNK) MAPK expression by blood leucocyte subsets and levels of serum Igs were measured in blood from adults with asthma and/or rhinoconjunctivitis (N = 28) and non-asthma (N = 10) (flow cytometry, microfluorenzymeimmunoassay). Peripheral blood mononuclear cells (PBMC) from allergic subjects were cultured for 10 days ± anti-CD40/recombinant IL-4 ± inhibitor of phos-P38. Culture supernatants were assayed for IgE (ELISA). Phos-p38 MAPK expression by all leucocyte subsets of allergic subjects was associated with serum IgE levels (p ≤ 0.01), after adjusting for cell counts, age, sex, race and smoking status (p ≤ 0.04). Leucocyte expression of phos-ERK and JNK did not correlate with IgE (p = 0.09-0.99). Instead, phos-ERK expression was associated with serum IgG. When PBMC from atopic subjects were cultured for 10 days with anti-CD40/rhIL-4, IgE levels were 26.2 ± 18 ng/mL. Inclusion of SB202190 (5-20 μg/mL), a specific inhibitor of phos-p38 MAPK, in culture suppressed IgE production in dose-dependent manner, with peak suppression obtained with SB202190 at 20 μg/mL (82.1% ± 11.8) (p = 0.0001), with virtually no cytotoxicity (<5%). Different MAPK pathways may be associated with IgE (p38) and IgG (ERK) responses. Phos-p38 MAPK can be a potential anti-allergy drug target.

APA Citation

Silverberg, Jonathan I.; Smith-Norowitz, Tamar A.; Kohlhoff, Stephan; and Joks, Rauno, "Phosphorylated p38 MAP kinase expression by leucocytes is increased in allergic humans and associated with IgE responses" (2024). GW Authored Works. Paper 4582.
https://hsrc.himmelfarb.gwu.edu/gwhpubs/4582

Department

Dermatology