Role of novel protein kinase C isoforms in Lyme arthritis

Ok Shin, Aruna K. Behera, Roderick T. Bronson, Linden T. Hu

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Inflammation caused by Borrelia burgdorferi infection occurs as a result of induction of pro-inflammatory cytokines from activation of multiple signalling pathways. It has previously been shown that mitogen-activated protein kinase (MAPK) and Janus kinase/signal transducer and activator of transcription signalling pathways are activated by B. burgdorferi in cultured human chondrocytes. Protein kinase C (PKC) signalling pathways are potential candidates that may control these downstream signalling pathways. Here we show that B. burgdorferi infection leads to phosphorylation and activation of novel PKC isoforms (PKC δ, ε, η and θ) in a time-dependent manner. A specific inhibitor of novel PKC isoforms blocked the induction of pro-inflammatory molecules in response to B. burgdorferi infection as did transient transfection of novel PKC dominant-negative plasmids into chondrocytes. B. burgdorferi-induced p38 MAPK phosphorylation was also significantly inhibited by an inhibitor of novel PKC isoforms, suggesting that PKC activation occurs upstream of p38 activation. In vivo, administration of an inhibitor of classical and novel PKC isoforms to C3H/HeN mice infected with B. burgdorferi resulted in significantly reduced ankle inflammation and swelling. In conclusion, these data suggest that novel PKC isoforms are specifically activated by B. burgdorferi infection and this can contribute to the regulation of inflammation in vitro and in vivo.

Original languageEnglish
Pages (from-to)1987-1996
Number of pages10
JournalCellular Microbiology
Volume9
Issue number8
DOIs
Publication statusPublished - 2007 Aug 1
Externally publishedYes

Fingerprint

Lyme Disease
Borrelia burgdorferi
Protein Kinase C
Protein Isoforms
Borrelia Infections
Chemical activation
Phosphorylation
Chondrocytes
Inflammation
Janus Kinases
Inbred C3H Mouse
Mitogen-Activated Protein Kinase Kinases
p38 Mitogen-Activated Protein Kinases
Transcription
Transducers
Ankle
Transfection
Swelling
Plasmids
Cytokines

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Microbiology

Cite this

Role of novel protein kinase C isoforms in Lyme arthritis. / Shin, Ok; Behera, Aruna K.; Bronson, Roderick T.; Hu, Linden T.

In: Cellular Microbiology, Vol. 9, No. 8, 01.08.2007, p. 1987-1996.

Research output: Contribution to journalArticle

Shin, Ok ; Behera, Aruna K. ; Bronson, Roderick T. ; Hu, Linden T. / Role of novel protein kinase C isoforms in Lyme arthritis. In: Cellular Microbiology. 2007 ; Vol. 9, No. 8. pp. 1987-1996.
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