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327 results on '"Smith-Norowitz, Tamar"'

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

Author

Silverberg, Jonathan I., Smith‐Norowitz, Tamar A., Kohlhoff, Stephan, and Joks, Rauno

Subjects
*MONONUCLEAR leukocytes, *IMMUNOGLOBULIN E, *MITOGEN-activated protein kinases, *LEUCOCYTES
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. [ABSTRACT FROM AUTHOR]

Published
2024
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47. CD4+ T effector memory cell responses in Chlamydia pneumoniae‐stimulated peripheral blood mononuclear cells in nonasthmatic subjects.

Author

Smith‐Norowitz, Tamar A., Shidid, Sarah, Norowitz, Yitzchok M., and Kohlhoff, Stephan

Subjects
*MONONUCLEAR leukocytes, *IMMUNOLOGIC memory, *Q fever, *CHLAMYDIA trachomatis, *KLEBSIELLA pneumoniae, *CHLAMYDIA, *RESPIRATORY infections
Abstract

Chlamydia pneumoniae (C. pneumoniae) is a gram‐negative intracellular bacterium that causes respiratory infection in humans, including subjects with or without asthma. C. pneumoniae activates cells (e.g., monocytes/macrophages) in vitro, and produces cytokines that may contribute to inflammatory responses observed in asthma. Immunological differences exist between subjects with or without asthma, with regard to host responses to C. pneumoniae. The heterogeneity and subsequent diverse pathophysiology of asthma can be better understood by analyzing the repertoire of T‐cell subpopulations; the most common distinction between different asthma endotypes includes cytokines produced by CD4+ cells (T helper (Th)2 high vs. Th2 low). [ABSTRACT FROM AUTHOR]

Published
2022
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