The anti-allergic drug histaglobin inhibits NF-kappaB nuclear translocation and down-regulates proinflammatory cytokines.
The transcription factor NF-kappaB is the central regulator for the expression of various genes involved in inflammation, infection and immune response including the genes for IL-1beta, TNF-alpha, IL-6 and leukocyte adhesion molecules. Here, we show that the anti-allergic drug histaglobin down-regulates the release of IL-1beta, TNF-alpha, IL-6 and IL-10 in human peripheral blood mononuclear cell cultures. This down-regulatory effect becomes even more pronounced when the cultures are simultaneously activated with the T-lymphocyte mitogen phytohemagglutinin (PHA) or with the B-lymphocyte and macrophage activator lipopeptide (P(3)CSK(4)). We also demonstrate that histaglobin inhibits the nuclear translocation of NF-kappaB in response to TNF-alpha or lipopolysaccharide (LPS) in bone marrow-derived macrophages of Balb/c mice. The inhibitory effect of histaglobin on NF-kappaB activation and cytokine release might be responsible for its anti-allergic effect as demonstrated in clinical studies.
Ayoub
M
M
Institut für Molekulare Medizin und Zellforschung, AG Tumorimmunologie/Vakzine, Medizinische Fakultät der Universität Freiburg, D-79104, Freiburg, Germany.
Mittenbühler
K
K
Sütterlin
B W
BW
Bessler
W G
WG
D018926:Anti-Allergic Agents / Q000494:pharmacology*; D001854:Bone Marrow Cells / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis*; D015536:Down-Regulation / Q000187:drug effects; D004338:Drug Combinations; D005455:Fluorescent Antibody Technique; D006632:Histamine / Q000494:pharmacology*; D006801:Humans; D007202:Indicators and Reagents; D007375:Interleukin-1 / Q000096:biosynthesis; D016753:Interleukin-10 / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D014178:Translocation, Genetic / Q000187:drug effects*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D005719:gamma-Globulins / Q000494:pharmacology*
D018926:Anti-Allergic Agents; D016207:Cytokines; D004338:Drug Combinations; D007202:Indicators and Reagents; D007375:Interleukin-1; D015850:Interleukin-6; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D005719:gamma-Globulins; D016753:Interleukin-10; C002114:Histaglobin; D006632:Histamine