Negative regulation of TLR signaling by G-CSF and ATP in leukocytes

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Various Toll-like receptors are expressed on human leukocytes such as neutrophils and monocytes, and play an important role in the innate immunity. Although the molecular mechanisms of Toll-like receptor-mediated cell activation have been increasingly understood, the positive and negative regulatory mechanisms on this system remain to be elusive. To elucidate the negative regulatory mechanisms by physiological molecules is particularly important for possible treatment of inflammation and tissue damage. We found that this system was positively regulated by granulocyte-macrophage colony-stimulating factor, interferon-alpha and interferon-gamma, and was negatively regulated by granulocyte colony-stimulating factor and ATP (adenosine tri-phosphate).