The influx of neutrophils into tissues in response to inflammatory stimuli involves C—X—C chemokines. Interleukin-1 (IL-1) stimulates chemokine production in vitro , but its role in vivo on chemokine production is not as clearly understood. We hypothesized that IL-1 mediates in vivo tissue C—X—C chemokine production induced by systemic lipopolysaccharide (LPS). IL-1 activity was blockedbyIL-1 receptor antagonist (IL-1Ra). Rats were injected with Salmonella typhi LPS (0.5 mg/kg) with and without prior administration of IL-1Ra. Cytokine-induced neutrophil chemoattractant-1 (CINC-1) and macrophage inflammatory protein-2 (MIP-2) protein and mRNA levels, tissue neutrophil accumulation, and indices of organ injury were measured. LPS administration resulted in increased plasma, lung, and liver IL-1β that was decreased by IL-1Ra. LPS also induced an increase in plasma, lung, and liver CINC-1 and MIP-2 protein and mRNA. However, IL-1Ra had no effect on LPS-induced plasma or lung tissue CINC-1 levels. In contrast, IL-1Ra pretreatment did significantly decrease CINC-1 protein expression in the liver (45% decrease) and MIP-2 protein expression in plasma (100% decrease), lung (72% decrease) and liver (100% decrease) compared to LPS-treated controls. Steady-state mRNA levels by Northern blot analysis of both CINC-1 and MIP-2 in lung and liver were similar to the protein findings. Pretreatment with IL-1Ra also resulted in a 47% and 59% decrease in lung and liver neutrophil accumulation, respectively, following LPS. In addition, indices of both lung and liver injury were decreased in animals pretreated with IL-1Ra. In summary, LPS induces IL-1β and MIP-2 expression in the lung and liver, both of which are IL-1 dependent. Although lung neutrophil accumulation in both lung and liver after LPS is also IL-1 mediated, lung CINC-1 levels were unaffected by IL-1Ra. These data suggest that IL-1 regulates tissue chemokine expression and neutrophil accumulation after LPS.
References
1.
Springer TATraffic signals for lymphocyte recirculation and leukocyte emigration: the multistep paradigm. Cell1994; 76: 301—314.
2.
Baggiolini M. , Dewald B., Moser B.Interleukin-8 and related chemotactic cytokines: CXC and CC chemokines. Adv Immunol1994; 55: 97—179.
3.
Luster FHChemokines — chemotactic cytokines that mediate inflammation . N Engl J Med1998; 338: 436—445.
4.
Shames BD, Zallen GS, McIntyre Jr RC et al. Chemokines as mediators of diseases related to surgical conditions . Shock2000; 14: 1—7.
5.
Dong W., Simeonova PP, Gallucci R. et al. Cytokine expression in hepatocytes: role of oxidant stress. J Interferon Cytokine Res1998; 18: 629—638.
6.
Kopydlowski KM, Salkowski CA, Cody MJ et al. Regulation of macrophage chemokine expression by lipopolysaccharide in vitro and in vivo . J Immunol1999; 163: 1537—1544.
7.
Mawet E., Shiratori Y., Hikiba Y. et al. Cytokine-induced neutrophil chemoattractant release from hepatocytes is modulated by Kupffer cells. Hepatology1996; 23: 353—358.
8.
Mercer-Jones MA, Shrotri MS, Peyton JC, Remick DG, Cheadle WGNeutrophil sequestration in liver and lung is differentially regulated by C—X—C chemokines during experimental peritonitis. Inflammation1999; 23: 305—319.
9.
Pennington HL , Wilce PA, Worrall S.Chemokine and cell adhesion molecule mRNA expression and neutrophil infiltration in lipopolysaccharide-induced hepatitis in ethanol-fed rats. Alcohol Clin Exp Res1998; 22: 1713—1718.
10.
Rovai LE, Herschman HR, Smith JBThe murine neutrophil-chemoattractant chemokines LIX, KC, and MIP-2 have distinct induction kinetics, tissue distributions, and tissue-specific sensitivities to glucocorticoid regulation in endotoxemia. J Leukoc Biol1998; 64: 494—502.
11.
Shanley TP, Schmal H., Warner RL et al. Requirement for C—X—C chemokines (macrophage inflammatory protein-2 and cytokine-induced neutrophil chemoattractant) in IgG immune complex-induced lung injury. J Immunol1997; 158: 3439—3448.
12.
Czermak BJ, Sarma V., Bless NM et al. In vitro and in vivo dependency of chemokine generation on C5a and TNF-α. J Immunol1999; 162: 2321—2325.
13.
Hall DJ, Brownlee C., Stiles CDInterleukin-1 is a potent regulator of JE and KC gene expression in quiescent BALB/c fibroblasts. J Cell Physiol1989; 141: 154—159.
14.
Hall DJ, Stiles CDPlatelet-derived growth factor-inducible genes respond differentially to at least two distinct intracellular second messengers. J Biol Chem1987; 262: 15302—15308.
15.
Kaplanski G. , Farnarier C., Kaplanski S. et al. Interleukin-1 induces interleukin-8 secretion from endothelial cells by a juxtacrine mechanism . Blood1994; 84: 4242—4248.
16.
Porat R., Poutsiaka DD, Miller LC, Granowitz EV, Dinarello CAInterleukin-1 (IL-1) receptor blockade reduces endotoxin and Borrelia burgdorferi-stimulated IL-8 synthesis in human mononuclear cells. FASEB J1992; 6: 2482.
17.
Shen XY, Hamilton TA, DiCorleto PEThrombin-induced expression of the KC gene in cultured aortic endothelial cells. Involvement of proteolytic activity and protein kinase C. Biochim Biophys Acta1990; 1049: 145—150.
18.
Shiratori Y. , Hikiba Y., Mawet E. et al. Modulation of KC/GRO protein (interleukin-8 related protein in rodents) release from hepatocytes by biologically active mediators. Biochem Biophys Res Commun1994 ; 203: 1398—1403.
19.
Hybertson BM , Jepson EK, Clarke JH, Spelts RJ, Repine JBInterleukin-1 stimulates rapid release of cytokine-induced neutrophil chemoattractant (CINC) in rat lungs. Inflammation1996; 20: 471—483.
20.
Koh Y., Hybertson BM, Jepson EK, Cho OJ, Repine JECytokine-induced neutrophil chemoattractant is necessary for interleukin-1 induced lung leak. J Appl Physiol1995; 79: 472—478.
21.
Megyeri P., Issekutz TB, Issekutz ACAn endotoxin-induced factor distinct from interleukin-1 and tumour necrosis factor alpha produced by the THP-1 human macrophage line stimulates polymorphonuclear leukocyte infiltration in vivo. J Leukoc Biol1990; 47: 70—78.
22.
Yoshimura T. , Matsushima K., Oppenheim JJ, Leonard EJNeutrophil chemotactic factor produced by lipopolysaccharide (LPS)-stimulated human blood mononuclear leukocytes: partial characterization and separation from interleukin 1 (IL 1). J Immunol1987; 139: 788—793.
23.
Sheridan BC , McIntyre RC, Agrafojo J. et al. Neutrophil depletion attenuates endotoxin-induced dysfunction of cGMPmediated pulmonary vasorelaxation . Am J Physiol1996; 271: L820—L828.
Henderson GS , Conary JT, Davidson JM et al. A reliable method for Northern blot analysis using synthetic oligonucleotide probes. Biotechniques1991; 10: 190—197.
26.
Chomczynski P., Sacchi N.Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem1987; 162: 156—159.
27.
Ohkawa H., Ohishi N., Yagi K.Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction . Anal Biochem1979; 95: 351—358.
28.
Mancilla J. , Garcia P., Dinarello CAThe interleukin-1 receptor antagonist can either reduce or enhance the lethality of Klebsiella pneumoniae sepsis in newborn rats. Infect Immun1993; 61: 926—932.
29.
Russell ME, Adams DH, Wyner LR et al. Early and persistent induction of monocyte chemoattractant protein 1 in rat cardiac allografts. Proc Natl Acad Sci USA1993; 90: 6086—6090.
30.
Arend WP, Malyak M., Guthridge CJ, Gabay C.Interleukin-1 receptor antagonist: role in biology. Annu Rev Immunol1998; 16: 27—55.
31.
Dinarello CABiologic basis for interleukin-1 in disease . Blood1996; 87: 2095—2147.
32.
Granowitz EV , Clark BD, Vannier E., Callahan MV, Dinarello CAEffect of interleukin-1 (IL-1) blockade on cytokine synthesis: I. IL-1 receptor antagonist inhibits IL- 1-induced cytokine synthesis and blocks the binding of IL-1 to its type II receptor on human monocytes. Blood1992 ; 79: 2356—2363.
33.
Schindler R. , Ghezzi P., Dinarello CAIL-1 induces IL-1. IV. IFNgamma suppresses IL-1 but not lipopolysaccharide-induced transcription of IL-1. J Immunol1990; 144: 2216—2222.
34.
Hirschfeld M. , Ma Y., Weis JH, Vogel SN, Weis JJRepurification of lipopolysaccharide eliminates signaling through both human and murine toll-like receptor 2. J Immunol2000; 165: 618—622.
35.
Awane M., Andres PG, Li DJ, Reinecker HCNF-kappa B-inducing kinase is a common mediator of IL-17-, TNF-alpha-, and IL-1 beta-induced chemokine promoter activation in intestinal epithelial cells . J Immunol1999; 162: 5337—5344.
36.
Blackwell TA , Holden EP, Blackwell TR, DeLarco JE, Christman JWCytokine-induced neutrophil chemoattractant mediates neutrophilic alveolitis in rats: association with nuclear factor κ B activation. Am J Respir Cell Mol Biol1994 ; 11: 464—472.
37.
Tebo JM, Datta S., Kishore R. et al. Interleukin-1-mediated stabilization of mouse KC mRNA depends on sequences in both 5'- and 3'-untranslated regions. J Biol Chem2000; 275: 12987—12993.
38.
Uehara T., Matsuno J., Kaneko M. et al. Transient nuclear factor kappaB (NF-kappaB) activation stimulated by interleukin-1beta may be partly dependent on proteasome activity, but not phosphorylation and ubiquitination of the IkappaBalpha molecule, in C6 glioma cells. Regulation of NF-kappaB linked to chemokine production. J Biol Chem1999; 274: 15875—15882.
39.
Fantuzzi G. , Dinarello CAThe inflammatory response in interleukin-1 beta-deficient mice: comparison with other cytokine-related knock-out mice . J Leukoc Biol1996; 59: 489—493.
40.
Fantuzzi G. , Zheng H., Faggioni FR et al. Effect of endotoxin in IL-1 beta-deficient mice. J Immunol1996 ; 157: 291—296.
41.
Parsey MV, Kaneko D., Shenkar R., Abraham E.Neutrophil apoptosis in the lung after hemorrhage or endotoxemia: apoptosis and migration are independent of IL-1beta. Clin Immunol1999; 91: 219—225.
42.
Fantuzzi G. , Sacco S., Ghezzi P., Dinarello CAPhysiological and cytokine responses in IL-1 beta-deficient mice after zymosaninduced inflammation . Am J Physiol1997; 273: R400—R406.
43.
Diab A., Abdalla H., Li HL et al. Neutralization of macrophage inflammatory protein 2 (MIP-2) and MIP-1alpha attenuates neutrophil recruitment in the central nervous system during experimental bacterial meningitis. Infect Immun1999; 67: 2590—2601.
44.
Ulich TR, Howard SC, Remick DR et al. Intratracheal administration of endotoxin and cytokines VI. antiserum to CINC inhibits acute inflammation. Am J Physiol1995; 268: L245—L250.
45.
Piccolo MT, Wang Y., Sannomiya P. et al. Chemotactic mediator requirements in lung injury following skin burns in rats. Exp Mol Pathol1999; 66: 220—226.
