ABSTRACT
Histamine affects the balance of T helper type 1 (Th1) and T helper type 2 (Th2) cytokines by shifting cytokine production from a Th1 to a Th2 pattern. Interleukin-13 (IL-13) is an important autacoid mediator that has been implicated in the development of allergic disease. This study was designed to investigate the mechanisms of regulation of IL-13 by histamine in Th2 cells. D10.G4.1 cells, a murine Th2 cell line, were treated with histamine (10(-8)-10(-4) M) and then activated with PMA (phorbol 12 myristate 13-acetate) plus ionomycin or alphaCD3. Levels of IL-13 production were then measured by enzyme-linked immunosorbent assay (ELISA) and semiquantitative reverse transcription-polymerase chain reaction (RT-PCR). Cells were pretreated with histamine receptor antagonists pyrilamine, ranitidine, cimetidine and thioperamide to determine the involvement of histamine receptors. Cells were also pretreated with protein kinase A (PKA) inhibitors N-[2-(methylaminoethyl)]-5-isoquinoline-sulfonamide (H-8) and Rp-diastereomer of adenosine cyclic 3'5'-phosphorothionate (Rp-cAMPS), and Janus kinase-signal transducer and activator of transcription (Jak-STAT) inhibitor tyrphostin AG490 prior to the addition of histamine. H-8 is an inhibitor of the catalytic subunit of PKA while Rp-cAMPS is an inhibitor of the regulatory subunit of PKA. Tyrphostin is an inhibitor of Jak2, Jak3, STATI, STAT3 and STAT5. Finally, cells were pretreated with IL-12, a monokine known to repress STAT6 DNA binding. We found that histamine dose-dependently enhanced IL-13 secretion and mRNA levels in Th2 cells via H1 and H2 receptors. Pretreatment of cells with H-8, Rp-cAMPS and tyrphostin prevented histamine-induced secretion and transcription of IL-13. Likewise, pretreatment of Th2 cells with IL-12 also reversed histamine's effects on IL-13 secretion from stimulatory to inhibitory. These observations suggest a role for PKA and the Jak-STAT pathway in histamine-mediated elevation of IL-13 secretion and transcription.
Subject(s)
Histamine/pharmacology , Interleukin-13/biosynthesis , Th2 Cells/metabolism , Animals , Cell Line , Clone Cells , Culture Media , Cyclic AMP/metabolism , Cyclic AMP-Dependent Protein Kinases/antagonists & inhibitors , Enzyme Inhibitors/pharmacology , Histamine Antagonists/pharmacology , Indicators and Reagents , Kinetics , Mice , RNA, Messenger/biosynthesis , Spleen/cytology , Spleen/drug effects , Spleen/metabolism , Th2 Cells/drug effects , Transcription, Genetic/drug effects , Up-Regulation/drug effectsSubject(s)
Diphtheria/immunology , Polyneuropathies/immunology , Acute Disease , Adult , Aged , Antibody Formation , Cause of Death , Diphtheria/complications , Diphtheria/diagnosis , Diphtheria/mortality , Female , Humans , Immunity, Cellular , Latvia/epidemiology , Male , Middle Aged , Polyneuropathies/diagnosis , Polyneuropathies/etiology , Polyneuropathies/mortalityABSTRACT
Forty-nine patients with acute viral hepatitis A and B were examined for the relationship of the blood content of individual lymphocyte subpopulations at the height of the disease to subsequent duration of the cytolytic syndrome (high activity of ALT). The duration of the cytolytic syndrome associated with viral hepatitis A was reversely related to the content of B lymphocytes and when associated with viral hepatitis B to the content of T cells--immunoregulator precursors (autorosette-forming cells). In both patterns of viral hepatitis, the duration of the cytolytic syndrome did not depend on the rate of lymphocyte sensitization to the inducer antigens (HAVAg, kHBsAg). Unlike viral hepatitis A, the duration of the cytolytic syndrome in viral hepatitis B was directly related to the rate of lymphocyte sensitization to hepatic lipoprotein.
Subject(s)
B-Lymphocytes/immunology , Hepatitis A/immunology , Hepatitis B/immunology , T-Lymphocytes/immunology , Cytotoxicity, Immunologic , Humans , Leukocyte Count , Rosette FormationABSTRACT
In 272 patients with virus hepatitis A and B the content of theophylline-sensitive lymphocytes (T-suppressors) and theophylline-resistant lymphocytes (T-helpers) in the peripheral blood was determined. Differences in the content of T-suppressors in cases of acute virus hepatitis A and B with an equal degree of severity were revealed: at the peak of hepatitis A infection in the mild form of the disease the number of the cells was decreased, while at the peak of hepatitis B infection an increase in their number was observed in the mild and moderate forms of the disease and a decrease, in the severe form of the disease. In chronic persistent hepatitis a decrease in the content of T-suppressors and an increase in the content of T-helpers were observed, and in chronic active hepatitis (at the period of remission) and increase in the T-helpers occurred. Changes in the content of the cells of both types are not characteristic of HBsAg carriership.
Subject(s)
Hepatitis A/immunology , Hepatitis B/immunology , Carrier State/immunology , Hepatitis, Chronic/immunology , Humans , Leukocyte Count , T-Lymphocytes, Helper-Inducer/drug effects , T-Lymphocytes, Helper-Inducer/immunology , T-Lymphocytes, Regulatory/drug effects , T-Lymphocytes, Regulatory/immunology , Theophylline/pharmacologyABSTRACT
The determination of the content of thermostable T-lymphocytes in the peripheral blood in 184 patients with acute virus hepatitis, as well as at the stage of the termination of the disease, has revealed the increased number of cells belonging to this subpopulation in all the groups under study. At the acute stage of the disease a rise in the number of thermostable T-cells is directly related to the severity of the process. Of different variants of the termination of hepatitis B, the highest content of thermostable T-cells is observed in chronic active hepatitis and chronic HBsAg carriership, while in chronic persistent hepatitis the content of thermostable T-cells is considerably lower.
