The flagellin-TLR5 axis

Therapeutic opportunities

Lucas Liaudet, Amitabha Deb, Pál Pacher, Jon G. Mabley, Kanneganti G K Murthy, Andrew L. Salzman, Csaba Szabo

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

Motile bacteria synthesize large-sized surface structures known as flagella through the ordered polymerization of protein subunits. Flagellin, a protein of 40-60 kDa, is the principal constituent of the flagellum; each flagellum consists of approximately 20,000 flagellin molecules. An alignment of the amino acid sequences from different Gram-negative species shows a high degree of similarity in the amino and carboxy terminal domains. In contrast, the central hypervariable regions of these proteins are quite divergent. Recent work reveals that - in addition to playing a role in bacterial adhesion - monomeric flagellin, a protein component of flagellated bacteria, can also act as a soluble immunostimulatory and proinflammatory factor, activating the immune/inflammatory axis via the Toll-like receptor 5-nuclear factor-κB axis. Monocytes and macrophages, as well as intestinal and pulmonary epithelial cells, respond to monomeric flagellin at low concentrations. Administration of flagellin at doses comparable to or lower than that of bacterial lipopolysaccharide (endotoxin) can induce prominent local and systemic immune/inflammatory responses in vivo. Recognition of the flagellin-TLR5 pathway offers novel opportunities for the experimental therapy of various forms of shock, sepsis, acute respiratory distress syndrome, bacterial inflammation and infection.

Original languageEnglish (US)
Pages (from-to)397-409
Number of pages13
JournalDrug News and Perspectives
Volume15
Issue number7
DOIs
StatePublished - Sep 2002
Externally publishedYes

Fingerprint

Flagellin
Flagella
Toll-Like Receptor 5
Therapeutics
Bacterial Adhesion
Bacteria
Investigational Therapies
Proteins
Adult Respiratory Distress Syndrome
Protein Subunits
Immunologic Factors
Bacterial Infections
Endotoxins
Polymerization
Lipopolysaccharides
Monocytes
Amino Acid Sequence
Shock
Sepsis
Epithelial Cells

ASJC Scopus subject areas

  • Pharmacology

Cite this

Liaudet, L., Deb, A., Pacher, P., Mabley, J. G., Murthy, K. G. K., Salzman, A. L., & Szabo, C. (2002). The flagellin-TLR5 axis: Therapeutic opportunities. Drug News and Perspectives, 15(7), 397-409. https://doi.org/10.1358/dnp.2002.15.7.840075

The flagellin-TLR5 axis : Therapeutic opportunities. / Liaudet, Lucas; Deb, Amitabha; Pacher, Pál; Mabley, Jon G.; Murthy, Kanneganti G K; Salzman, Andrew L.; Szabo, Csaba.

In: Drug News and Perspectives, Vol. 15, No. 7, 09.2002, p. 397-409.

Research output: Contribution to journalArticle

Liaudet, L, Deb, A, Pacher, P, Mabley, JG, Murthy, KGK, Salzman, AL & Szabo, C 2002, 'The flagellin-TLR5 axis: Therapeutic opportunities', Drug News and Perspectives, vol. 15, no. 7, pp. 397-409. https://doi.org/10.1358/dnp.2002.15.7.840075
Liaudet L, Deb A, Pacher P, Mabley JG, Murthy KGK, Salzman AL et al. The flagellin-TLR5 axis: Therapeutic opportunities. Drug News and Perspectives. 2002 Sep;15(7):397-409. https://doi.org/10.1358/dnp.2002.15.7.840075
Liaudet, Lucas ; Deb, Amitabha ; Pacher, Pál ; Mabley, Jon G. ; Murthy, Kanneganti G K ; Salzman, Andrew L. ; Szabo, Csaba. / The flagellin-TLR5 axis : Therapeutic opportunities. In: Drug News and Perspectives. 2002 ; Vol. 15, No. 7. pp. 397-409.
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