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Conference Paper: The mechanisms underlying sulfamethoxazole metaboites regulated cytokine production
Title | The mechanisms underlying sulfamethoxazole metaboites regulated cytokine production |
---|---|
Authors | |
Issue Date | 2008 |
Publisher | Canadian Society of Pharmacology and Therapeutics |
Citation | The 9th World Conference on Clinical Pharmacology and Therapeutics, Quebec, Canada, 27 July-1 August 2008. In Canadian Journal of Clinical Pharmacology, 2008, v. 15 n. 3, p. e611, abstract no. 408 How to Cite? |
Abstract | For many decades, sulphonamides together with
trimethoprim have been used as antimicrobial
agents against bacterial and protozoan infections in immunocompromised patients. During bacterial
infection, proinflammatory cytokines including
tumor necrosis factor-alpha (TNF-alpha) and
interleukin-6 (IL-6), as well as anti-inflammatory
cytokines such as IL-10 are produced by
macrophages. Here, we investigated the mechanisms
and effects of sulfamethoxazole metabolites, which
are related to hypersensitivity reactions, on cytokine
production in primary human differentiated blood
macrophages (PBMac). PBMac were incubated with
the drug metabolites for 30 minutes and followed by
the addition of bacterial endotoxin (LPS) for another
15 minutes to 3 hours. The results from the Real
time Quantitative RT-PCR showed that the mRNA
expressions of IL-6 and IL-10 in metabolites-treated
cells were downregulated, compared to the LPS
treatment alone. We also demonstrated the protein
levels of IL-6, IL-10 and TNF-alpha were
suppressed. To delineate the molecular mechanisms
involved in the metabolites-induced cytokine
production, we measured the activity levels of
mitogen-activated protein kinases (MAPK), which
are known to be key signaling modulators in
cytokine induction. The results illustrated that
sulfamethoxazole metabolites abrogated the LPSinduced
MAPK phosphorylation, concomitant
with their effects on cytokine downregulation.
Furthermore, sulfamethoxazole metabolites could
inhibit the LPS-activated nuclear factor-kappa B
(NF-kappa B) functions. In conclusion, our data
demonstrated that in addition to their
antimicrobial effects, sulfamethoxazole
metabolites may play a role in limiting the
propagation of uncontrolled inflammation, via the
suppression of MAPK and NF-kappa B activities,
in microbial infections. |
Persistent Identifier | http://hdl.handle.net/10722/62775 |
ISSN | 2020 SCImago Journal Rankings: 0.166 |
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Lau, ASY | en_HK |
dc.contributor.author | Li, CB | en_HK |
dc.contributor.author | Yim, HCH | en_HK |
dc.contributor.author | Rieder, MJ | en_HK |
dc.date.accessioned | 2010-07-13T04:08:55Z | - |
dc.date.available | 2010-07-13T04:08:55Z | - |
dc.date.issued | 2008 | en_HK |
dc.identifier.citation | The 9th World Conference on Clinical Pharmacology and Therapeutics, Quebec, Canada, 27 July-1 August 2008. In Canadian Journal of Clinical Pharmacology, 2008, v. 15 n. 3, p. e611, abstract no. 408 | - |
dc.identifier.issn | 1198-581X | - |
dc.identifier.uri | http://hdl.handle.net/10722/62775 | - |
dc.description.abstract | For many decades, sulphonamides together with trimethoprim have been used as antimicrobial agents against bacterial and protozoan infections in immunocompromised patients. During bacterial infection, proinflammatory cytokines including tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6), as well as anti-inflammatory cytokines such as IL-10 are produced by macrophages. Here, we investigated the mechanisms and effects of sulfamethoxazole metabolites, which are related to hypersensitivity reactions, on cytokine production in primary human differentiated blood macrophages (PBMac). PBMac were incubated with the drug metabolites for 30 minutes and followed by the addition of bacterial endotoxin (LPS) for another 15 minutes to 3 hours. The results from the Real time Quantitative RT-PCR showed that the mRNA expressions of IL-6 and IL-10 in metabolites-treated cells were downregulated, compared to the LPS treatment alone. We also demonstrated the protein levels of IL-6, IL-10 and TNF-alpha were suppressed. To delineate the molecular mechanisms involved in the metabolites-induced cytokine production, we measured the activity levels of mitogen-activated protein kinases (MAPK), which are known to be key signaling modulators in cytokine induction. The results illustrated that sulfamethoxazole metabolites abrogated the LPSinduced MAPK phosphorylation, concomitant with their effects on cytokine downregulation. Furthermore, sulfamethoxazole metabolites could inhibit the LPS-activated nuclear factor-kappa B (NF-kappa B) functions. In conclusion, our data demonstrated that in addition to their antimicrobial effects, sulfamethoxazole metabolites may play a role in limiting the propagation of uncontrolled inflammation, via the suppression of MAPK and NF-kappa B activities, in microbial infections. | - |
dc.language | eng | en_HK |
dc.publisher | Canadian Society of Pharmacology and Therapeutics | - |
dc.relation.ispartof | Canadian Journal of Clinical Pharmacology | - |
dc.title | The mechanisms underlying sulfamethoxazole metaboites regulated cytokine production | en_HK |
dc.type | Conference_Paper | en_HK |
dc.identifier.email | Li, CB: jamesli@graduate.hku.hk | en_HK |
dc.identifier.email | Yim, HCH: chhyim@graduate.hku.hk | en_HK |
dc.identifier.email | Lau, ASY: asylau@hku.hk | en_HK |
dc.identifier.authority | Li, CB=rp00496 | en_HK |
dc.identifier.authority | Lau, ASY=rp00474 | en_HK |
dc.identifier.hkuros | 143321 | en_HK |
dc.identifier.volume | 15 | - |
dc.identifier.issue | 3 | - |
dc.identifier.spage | e611, abstract no. 408 | - |
dc.identifier.epage | e611, abstract no. 408 | - |
dc.identifier.issnl | 1198-581X | - |