Abstracts (complete list) - Wissenschaft Online

Paul Gutwein, Anja Schramme, Liliana Schäfer, Hermann-Josef Gröne, Mohamed
Sadek, Ingeborg Hauser, Josef Pfeilschifter
The role of transmembrane and released CXCL16 during
inflammatory processes in the kidney
Inflammatory cell infiltrates are a hallmark of chronic kidney diseases (CKDs).
Understanding the molecular mechanism that regulate renal leukocyte recruitment
suggest chemokines and chemokine receptors as new targets for specific
pharmacological intervention. In vitro we have analyzed the expression, localization and
cleavage of CXCL16 in human renal mesangial cells. We can show that CXCL16
expression is found in the nucleus, in lysosomes and in the endoplasmatic reticulum
whereas no colocalization of CXCL16 with the Golgi stacks could be observed.
Interestingly, when we stimulated the cells with INF-g, IL1b or LPS we could induce the
expression of CXCL16. Additionally the application of IFN-g resulted in increased
amounts of soluble CXCL16 in the supernatant of the cells. By using RNA interference
we could inhibit ADAM10 and ADAM17 very efficiently and we clearly can show that both
metalloproteinases are involved in the constitutive as well as in the inducible release of
CXCL16 from mesangial cells. Interestingly the expression of endogenous CXCL16 was
not influenced by the knockdown of ADAM10 or ADAM17 suggesting that both
metalloproteinases may play important function in the transport of CXCL16.
In vivo we found CXCL16 expression in the healthy kidney mainly in podocytes and
distal tubular cells. Furthermore increased amounts of CXCL16 were found in the
glomerulus of kidney transplanted patients. Importantly CXCR6 expressing immune
cells were found in high numbers in the inflamed kidney of transplanted patients.
Analyzing urine samples of patients with inflammatory kidney diseases, we found
increased amounts of soluble CXCL16 compared to healthy volunteers. Taken together
this data suggest an important participation of the chemokine CXCL16 and its receptor
CXCR6 in the recruitment of leukocytes into the kidney during inflammatory processes.