Gene microarray analyses of daboia russelli russelli daboiatoxin treatment of THP-1 human macrophages infected with burkholderia pseudomallei

R. Perumal Samy, J. Manikandan, Pachiappan Arjunan, E. E. Ooi, L. T. Aw, B. G. Stiles, O. L. Franco, M. Kandasamy, K. M. Mathi, G. Rane, K. S. Siveen, C. Arunachalam, M. E. Zayed, S. A. Alharbi, A. P. Kumar, G. Sethi, L. H.K. Lim, V. T. Chow

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Burkholderia pseudomallei is the causative agent of melioidosis and represents a potential bioterrorism threat. In this study, the transcriptomic responses of B. pseudomallei infection of a human macrophage cell model were investigated using whole-genome microarrays. Gene expression profiles were compared between infected THP-1 human monocytic leukemia cells with or without treatment with Daboia russelli russelli daboiatoxin (DRRDbTx) or ceftazidime (antibiotic control). Microarray analyses of infected and treated cells revealed differential upregulation of various inflammatory genes such as interleukin-1 (IL-1), IL-6, tumor necrosis factor-alpha (TNF-α), cyclooxygenase (COX-2), vascular endothelial growth factor (VEGF), chemokine C-X-C motif ligand 4 (CXCL4), transcription factor p65 (NF-kB); and several genes involved in immune and stress responses, cell cycle, and lipid metabolism. Moreover, following DRR-DbTx treatment of infected cells, there was enhanced expression of the tolllike receptor 2 (TLR-2) mediated signaling pathway involved in recognition and initiation of acute inflammatory responses. Importantly, we observed that highly inflammatory cytokine gene responses were similar in infected cells exposed to DRR-DbTx or ceftazidime after 24 h. Additionally, there were increased transcripts associated with cell death by caspase activation that can promote host tissue injury. In summary, the transcriptional responses during B. pseudomallei infection of macrophages highlight a broad range of innate immune mechanisms that are activated within 24 h post-infection. These data provide insights into the transcriptomic kinetics following DRR-DbTx treatment of human macrophages infected with B. pseudomallei.

Original languageEnglish (US)
Pages (from-to)961-974
Number of pages14
JournalCurrent Molecular Medicine
Volume15
Issue number10
DOIs
StatePublished - Dec 1 2015

Fingerprint

Burkholderia pseudomallei
Macrophages
Microarray Analysis
Microarrays
Genes
Burkholderia Infections
Ceftazidime
Transcription Factor RelA
Bioterrorism
Cells
CXC Chemokines
NF-kappa B
Melioidosis
Vascular Endothelial Growth Factor C
Cell death
Prostaglandin-Endoperoxide Synthases
Caspases
Interleukin-1
Gene expression
Vascular Endothelial Growth Factor A

Keywords

  • Burkholderia pseudomallei
  • Daboia russelli russelli daboiatoxin
  • Gene expression
  • Human macrophages
  • Pro-inflammatory cytokines
  • Venom protein

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology

Cite this

Gene microarray analyses of daboia russelli russelli daboiatoxin treatment of THP-1 human macrophages infected with burkholderia pseudomallei. / Perumal Samy, R.; Manikandan, J.; Arjunan, Pachiappan; Ooi, E. E.; Aw, L. T.; Stiles, B. G.; Franco, O. L.; Kandasamy, M.; Mathi, K. M.; Rane, G.; Siveen, K. S.; Arunachalam, C.; Zayed, M. E.; Alharbi, S. A.; Kumar, A. P.; Sethi, G.; Lim, L. H.K.; Chow, V. T.

In: Current Molecular Medicine, Vol. 15, No. 10, 01.12.2015, p. 961-974.

Research output: Contribution to journalArticle

Perumal Samy, R, Manikandan, J, Arjunan, P, Ooi, EE, Aw, LT, Stiles, BG, Franco, OL, Kandasamy, M, Mathi, KM, Rane, G, Siveen, KS, Arunachalam, C, Zayed, ME, Alharbi, SA, Kumar, AP, Sethi, G, Lim, LHK & Chow, VT 2015, 'Gene microarray analyses of daboia russelli russelli daboiatoxin treatment of THP-1 human macrophages infected with burkholderia pseudomallei', Current Molecular Medicine, vol. 15, no. 10, pp. 961-974. https://doi.org/10.2174/1566524016666151123114123
Perumal Samy, R. ; Manikandan, J. ; Arjunan, Pachiappan ; Ooi, E. E. ; Aw, L. T. ; Stiles, B. G. ; Franco, O. L. ; Kandasamy, M. ; Mathi, K. M. ; Rane, G. ; Siveen, K. S. ; Arunachalam, C. ; Zayed, M. E. ; Alharbi, S. A. ; Kumar, A. P. ; Sethi, G. ; Lim, L. H.K. ; Chow, V. T. / Gene microarray analyses of daboia russelli russelli daboiatoxin treatment of THP-1 human macrophages infected with burkholderia pseudomallei. In: Current Molecular Medicine. 2015 ; Vol. 15, No. 10. pp. 961-974.
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AU - Arjunan, Pachiappan

AU - Ooi, E. E.

AU - Aw, L. T.

AU - Stiles, B. G.

AU - Franco, O. L.

AU - Kandasamy, M.

AU - Mathi, K. M.

AU - Rane, G.

AU - Siveen, K. S.

AU - Arunachalam, C.

AU - Zayed, M. E.

AU - Alharbi, S. A.

AU - Kumar, A. P.

AU - Sethi, G.

AU - Lim, L. H.K.

AU - Chow, V. T.

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