| First Author | Chen W | Year | 2009 |
| Journal | J Immunol | Volume | 183 |
| Issue | 12 | Pages | 7870-6 |
| PubMed ID | 20007572 | Mgi Jnum | J:306772 |
| Mgi Id | MGI:6708151 | Doi | 10.4049/jimmunol.0901028 |
| Citation | Chen W, et al. (2009) IL-13R alpha 2 membrane and soluble isoforms differ in humans and mice. J Immunol 183(12):7870-6 |
| abstractText | Although mice have nanogram per milliliter serum levels of soluble (s) IL-13Ralpha2, humans lack sIL-13Ralpha2 in serum. Our data provide a mechanism for this biological divergence. In mice, discrete transcripts encoding soluble and membrane forms of IL-13Ralpha2 are generated by alternative splicing. We used small interfering RNA to specifically deplete the transcript encoding membrane (mem) IL-13Ralpha2 (full-length) or sIL-13Ralpha2 (DeltaEx10) in murine cells. Depletion of the full-length transcript decreased memIL-13Ralpha2 but had no effect on the level of sIL-13Ralpha2 in cell supernatants at baseline or following cytokine stimulation. Depletion of the DeltaEx10 transcript decreased sIL-13Ralpha2 in supernatants at baseline and following stimulation. In contrast to mice, we were unable to find a transcript encoding sIL-13Ralpha2 in humans and siRNA-mediated depletion of full-length IL-13Ralpha2 decreased both sIL-13Ralpha2 and memIL-13Ralpha2 in human cells. Inhibition of matrix metalloproteinases (MMP)/MMP-8 abolished production of sIL-13Ralpha2 from human cells. Thus, sIL-13Ralpha2 is derived exclusively from the memIL-13Ralpha2 transcript in humans through MMPs/MMP-8 cleavage of memIL-13Ralpha2, supporting a limited role for sIL-13Ralpha2 in humans and highlighting the potential importance of memIL-13Ralpha2 in human immunity. These observations require consideration when results of murine IL-13 studies are applied to humans. |
