Gene transcription through activation of G-protein-coupled chemoattractant receptors

Receptors for leukocyte chemoattractants, including chemokines, are traditionally considered to be responsible for the activation of special leukocyte functions such as chemotaxis, degranulation, and the release of superoxide anions. Recently, these G-protein-coupled serpentine receptors have been found to transduce signals leading to gene transcription and translation in leukocytes. Transcription factors, such as NF kappa B and AP-1, are activated upon stimulation of the cells with several chemoattractants at physiologically relevant concentrations. Activation of transcription factors through these receptors involves G-protein coupling and the activation of protein kinases. The underlying signaling pathways appear to be different from those utilized by TNF-alpha, a better characterized cytokine that induces the transcription of immediate-early genes. Chemoattractants stimulate the expression of several inflammatory cytokines and chemokines, which in turn may activate their respective receptors and initiate an autocrine regulatory mechanism for persistent cytokine and chemokine gene expression.