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. 2003 Jun;12(3):179–183. doi: 10.1080/0962935031000134905

Role of interleukin-15 and interleukin-18 in the secretion of sIL-6R and sgp130 by human neutrophils.

E Jablonska 1, M Marcinczyk 1
PMCID: PMC1781607  PMID: 12857602

Abstract

BACKGROUND: Available data indicate that neutrophils (PMN) produce a wide range of cytokines with the potential to modulate immune response. Recent investigation have shown that interleukin (IL)-15 and IL-18 potentiated several functions of normal neutrophils. It has been reported that IL-18-induced cytokine production may be significantly enhanced by coincident addition of IL-15. AIMS: In the present study we compared the effect of recombinant human (rh)IL-15 and rhIL-18 as well as effect of a rhIL-15 and rhIL-18 combination on the induction secretion of sIL-6Ralpha and sgp130 by human neutrophils. METHODS: PMN were isolated from heparinized whole blood of healthy persons. The PMN were cultured for 18 h at 37 degrees C in a humidified incubator with 5% CO(2). rhIL-15 and/or rhIL-18 and lipopolysaccharide were tested to PMN stimulation. The culture supernatants of PMN were removed and examined for the presence of sIL-6R and sgp130 by human enzyme-linked immunosorbent assay kits. Cytoplasmic protein fractions of PMN were analysed for the presence of sIL-6R and sgp130 by western blotting using monoclonal antibodies capable of detecting these proteins. Cells were lysed and cytoplasmic proteins were electrophoresed on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The resolved proteins were transferred onto nitrocellulose and incubated with the primary monoclonal antibodies anti-sIL-6R and anti-sgp130. The membranes were incubated at room temperature with alkaline phosphatase anti-mouse immunoglobulin G. Immunoreactive protein bans were visualized by an AP Conjugate Substrate Kit. RESULTS AND CONCLUSIONS: The results of our investigation revealed that IL-15 alone, similarly to IL-18, has no significant ability for the regulation of both soluble IL-6 receptors, sIL-6R and sgp130, released by human neutrophils. It is interesting to note that the secretion of sgp130 was changed after PMN stimulation with rhIL-15 in the presence of rhIL-18. The combination of rhIL-15 and rhIL-18 was shown to induce PMN to secretion relatively higher amounts of sgp130 compared with the stimulation of PMN with rhIL-15 alone and rhIL-18 alone. The results obtained suggest that IL-15 and IL-18, belonging to the inflammatory cytokines, through the regulation of sgp130 secretion must be also considered as anti-inflammatory mediators that may influence the balance reactions mediated by the IL-6 cytokine family.

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Selected References

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  1. Cassatella M. A. The production of cytokines by polymorphonuclear neutrophils. Immunol Today. 1995 Jan;16(1):21–26. doi: 10.1016/0167-5699(95)80066-2. [DOI] [PubMed] [Google Scholar]
  2. Fehniger T. A., Shah M. H., Turner M. J., VanDeusen J. B., Whitman S. P., Cooper M. A., Suzuki K., Wechser M., Goodsaid F., Caligiuri M. A. Differential cytokine and chemokine gene expression by human NK cells following activation with IL-18 or IL-15 in combination with IL-12: implications for the innate immune response. J Immunol. 1999 Apr 15;162(8):4511–4520. [PubMed] [Google Scholar]
  3. Girard D., Paquet M. E., Paquin R., Beaulieu A. D. Differential effects of interleukin-15 (IL-15) and IL-2 on human neutrophils: modulation of phagocytosis, cytoskeleton rearrangement, gene expression, and apoptosis by IL-15. Blood. 1996 Oct 15;88(8):3176–3184. [PubMed] [Google Scholar]
  4. Jablonska E., Izycka A., Jablonska J., Wawrusiewicz N., Piecuch J. Role of IL-18 in the secretion of Il-1beta, sIL-1RII, and IL-1Ra by human neutrophils. Immunol Invest. 2001 Aug;30(3):221–229. doi: 10.1081/imm-100105066. [DOI] [PubMed] [Google Scholar]
  5. Jablonska E., Jablonski J. Effect of IL-18 on the release of IL-6 and its soluble receptors: sIL-6Ralpha and sgp130 by human neutrophils. Immunol Invest. 2002 Aug-Nov;31(3-4):159–167. doi: 10.1081/imm-120016237. [DOI] [PubMed] [Google Scholar]
  6. Jablonska E., Jablonski J., Holownia A. Role of neutrophils in release of some cytokines and their soluble receptors. Immunol Lett. 1999 Dec 1;70(3):191–197. doi: 10.1016/s0165-2478(99)00148-0. [DOI] [PubMed] [Google Scholar]
  7. Jablonska E., Piotrowski L., Kiluk M., Jablonski J., Grabowska Z., Markiewicz W. Effect of IL-15 on the secretion of IL-1beta, IL-1Ra and sIL-1RII by PMN from cancer patients. Cytokine. 2001 Dec 7;16(5):173–177. doi: 10.1006/cyto.2001.0931. [DOI] [PubMed] [Google Scholar]
  8. Jones S. A., Horiuchi S., Topley N., Yamamoto N., Fuller G. M. The soluble interleukin 6 receptor: mechanisms of production and implications in disease. FASEB J. 2001 Jan;15(1):43–58. doi: 10.1096/fj.99-1003rev. [DOI] [PubMed] [Google Scholar]
  9. Leung B. P., Culshaw S., Gracie J. A., Hunter D., Canetti C. A., Campbell C., Cunha F., Liew F. Y., McInnes I. B. A role for IL-18 in neutrophil activation. J Immunol. 2001 Sep 1;167(5):2879–2886. doi: 10.4049/jimmunol.167.5.2879. [DOI] [PubMed] [Google Scholar]
  10. McDonald P. P., Russo M. P., Ferrini S., Cassatella M. A. Interleukin-15 (IL-15) induces NF-kappaB activation and IL-8 production in human neutrophils. Blood. 1998 Dec 15;92(12):4828–4835. [PubMed] [Google Scholar]
  11. McInnes I. B., Gracie J. A., Leung B. P., Wei X. Q., Liew F. Y. Interleukin 18: a pleiotropic participant in chronic inflammation. Immunol Today. 2000 Jul;21(7):312–315. doi: 10.1016/s0167-5699(00)01648-0. [DOI] [PubMed] [Google Scholar]
  12. Mori A., Suko M., Kaminuma O., Inoue S., Ohmura T., Nishizaki Y., Nagahori T., Asakura Y., Hoshino A., Okumura Y. IL-15 promotes cytokine production of human T helper cells. J Immunol. 1996 Apr 1;156(7):2400–2405. [PubMed] [Google Scholar]
  13. Nishimura H., Yajima T., Naiki Y., Tsunobuchi H., Umemura M., Itano K., Matsuguchi T., Suzuki M., Ohashi P. S., Yoshikai Y. Differential roles of interleukin 15 mRNA isoforms generated by alternative splicing in immune responses in vivo. J Exp Med. 2000 Jan 3;191(1):157–170. doi: 10.1084/jem.191.1.157. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Smith X. G., Bolton E. M., Ruchatz H., Wei X., Liew F. Y., Bradley J. A. Selective blockade of IL-15 by soluble IL-15 receptor alpha-chain enhances cardiac allograft survival. J Immunol. 2000 Sep 15;165(6):3444–3450. doi: 10.4049/jimmunol.165.6.3444. [DOI] [PubMed] [Google Scholar]

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