1) Gram-negative bacteria release
lipopolysaccharide (LPS; endotoxin) from the outer membrane of their cell wall.
2) The LPS binds to a pair of TLR-4s on defense cells such as macrophages and dendritic cells. LPS also binds to LPS-binding protein in the plasma and tissue fluid. The LPS-binding protein promotes the binding of LPS to the CD14 receptors. At that point the LPS-binding protein comes off and the LPS-CD14 bind to TLR-4.
3) The binding of LPS to TLR-4 enables regulatory molecules within the cell - Mal, MyD88, Tram,
and Trif - to trigger reactions that activate a master regulator of inflammation
called NF-kappa B. Activated NF-kappa B enters the cell's nucleus and switches
on genes coding for cytokines such as:
4) Cytokine genes are transcribed into mRNA molecules that goe to the cytoplasm to be translated into inflammatory cytokines that are subsequently secreted from the cell.a. Interleukin-1 (IL-1) and Tumor necrosis factor-alpha (TNF-alpha): enhance inflammatory responses;
b. Interleukin-8 (IL-8): aids in the ability of white blood cells to leave the blood vessels and enter the tissue; a chemoattractant for phagocytes;
c. Interleukin-6 (IL-6) promotes B-lymphocyte activity; and
d. Interleukin-12 (IL-12): promotes T-lymphocyte activity. (5)
Flash animation illustrating Toll-Like Receptors Responding
to Lipopolysaccharide (LPS)
from the Gram-Negative Cell Wall and
Signaling the Synthesis
Inflammatory Cytokines.swf by Gary E. Kaiser, Ph.D.
Professor of Microbiology,
The Community College of Baltimore County, Catonsville Campus
This work is licensed under a Creative Commons Attribution 4.0 International License.
Based on a work at http://faculty.ccbcmd.edu/~gkaiser/index.html.
Last updated: August, 2018
Please send comments and inquiries to Dr.
Gary Kaiser