RESUMO
Chemokine receptors induce cell migration, but the molecular basis of the signal cascade involved is not completely understood. Therefore, we investigated here the molecular mechanisms of CCL3-, CCL5- and CCL8-induced cells migration and investigated whether the Janus kinase/signal transducer and activator of transcription (STAT) signalling pathway is involved. Some STAT3 inhibitors, like Cucurbitacin I, destroy the actin cytoskeleton inside the cells and therefore prevent any cellular migration. However, for inhibitors that do not affect the actin cytoskeleton or induce cell death, we show that chemokine-induced cell migration is not dependent on activation of Janus kinase 2 or STAT3.
Assuntos
Quimiocina CCL3/metabolismo , Quimiocina CCL5/metabolismo , Quimiocina CCL8/metabolismo , Quimiotaxia , Janus Quinase 2/metabolismo , Fator de Transcrição STAT3/metabolismo , Animais , Células CHO , Movimento Celular , Sobrevivência Celular , Quimiocina CCL3/genética , Quimiocina CCL5/genética , Quimiocina CCL8/genética , Cricetinae , Células HeLa , Humanos , Janus Quinase 2/genética , Fator de Transcrição STAT3/genética , Transdução de Sinais , Ativação TranscricionalRESUMO
The molecular signalling pathway of cell migration and whether it can occur independently of the release of intracellular calcium is still not completely understood. Therefore we investigated here the molecular mechanisms of CCL3 induced cell migration and the importance of intracellular calcium for chemotaxis in more detail. We show that CCL3 induced cell migration is dependent on activation of PLC. Several PKC inhibitors block the release of intracellular calcium independently of CCL3 activation and do not affect cell migration. This confirms that the release of intracellular calcium is not necessary for chemotaxis towards CCL3 and that PKC inhibitors should be used with caution in calcium release assays.
