PMID- 15753253 OWN - NLM STAT- MEDLINE DCOM- 20050819 LR - 20181113 IS - 1071-412X (Print) IS - 1098-6588 (Electronic) IS - 1071-412X (Linking) VI - 12 IP - 3 DP - 2005 Mar TI - Specific inhibitory action of anisodamine against a staphylococcal superantigenic toxin, toxic shock syndrome toxin 1 (TSST-1), leading to down-regulation of cytokine production and blocking of TSST-1 toxicity in mice. PG - 399-408 AB - Toxic shock syndrome toxin 1 (TSST-1), produced by Staphylococcus aureus (including methicillin-resistant S. aureus), is a superantigenic toxin responsible for toxic shock syndrome as well as neonatal TSS-like exanthematous disease. TSST-1 exhibits its deleterious effects by leading to the abnormal proliferation of, e.g., Vbeta2+ T cells and overproduction of proinflammatory cytokines. In the present study we examined the inhibitory effect of a Chinese herbal extract, anisodamine, on TSST-1 using human peripheral blood mononuclear cells (PBMCs). Anisodamine inhibited the production of proinflammatory cytokines better than interleukin-10 (an anti-inflammatory cytokine). The inhibitory effect of anisodamine was greater than that of any tropane alkaloid examined. Anisodamine acted directly on both monocytes and T cells in human PBMCs, and the effect was confirmed at the transcriptional level. Inhibition of NF-kappaB activation was also demonstrated. In contrast, no significant inhibition of Vbeta2+ T-cell proliferation was observed. In mice injected with TSST-1, anisodamine treatment significantly decreased serum proinflammatory cytokine levels and prevented TSST-1-induced death. These results suggest that anisodamine specifically acts against the production of cytokines (inflammatory cytokines in particular) and not against Vbeta2+ T-cell proliferation and that anisodamine may have a beneficial effect on TSST-1-associated disease. FAU - Nakagawa, Saori AU - Nakagawa S AD - Division of Bacteriology, Department of Infectious Disease Control and International Medicine, Niigata University Graduate School of Medical and Dental Sciences, 757 Ichibanchou, Asahimachidori, Niigata 951-8510, Japan. FAU - Kushiya, Koji AU - Kushiya K FAU - Taneike, Ikue AU - Taneike I FAU - Imanishi, Ken'ichi AU - Imanishi K FAU - Uchiyama, Takehiko AU - Uchiyama T FAU - Yamamoto, Tatsuo AU - Yamamoto T LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Clin Diagn Lab Immunol JT - Clinical and diagnostic laboratory immunology JID - 9421292 RN - 0 (Bacterial Toxins) RN - 0 (Cytokines) RN - 0 (Drugs, Chinese Herbal) RN - 0 (Enterotoxins) RN - 0 (Solanaceous Alkaloids) RN - 0 (Superantigens) RN - 0 (enterotoxin F, Staphylococcal) RN - 01343Q8EL8 (anisodamine) SB - IM MH - Animals MH - Bacterial Toxins/*antagonists & inhibitors MH - Cell Proliferation/drug effects MH - Cytokines/antagonists & inhibitors/*biosynthesis MH - Down-Regulation/*drug effects/genetics MH - Drugs, Chinese Herbal/pharmacology MH - Enterotoxins/*antagonists & inhibitors MH - Humans MH - Leukocytes, Mononuclear/drug effects MH - Mice MH - Monocytes/drug effects MH - Solanaceous Alkaloids/*pharmacology MH - Superantigens MH - T-Lymphocytes/cytology/drug effects/immunology MH - Transcription, Genetic/drug effects PMC - PMC1065205 EDAT- 2005/03/09 09:00 MHDA- 2005/08/20 09:00 PMCR- 2005/03/01 CRDT- 2005/03/09 09:00 PHST- 2005/03/09 09:00 [pubmed] PHST- 2005/08/20 09:00 [medline] PHST- 2005/03/09 09:00 [entrez] PHST- 2005/03/01 00:00 [pmc-release] AID - 12/3/399 [pii] AID - 0284-04 [pii] AID - 10.1128/CDLI.12.3.399-408.2005 [doi] PST - ppublish SO - Clin Diagn Lab Immunol. 2005 Mar;12(3):399-408. doi: 10.1128/CDLI.12.3.399-408.2005.