Interleukin 18 inhibits osteoclast formation via T cell production of granulocyte macrophage colony-stimulating factor

The Journal of Clinical Investigation
N J HorwoodM T Gillespie

Abstract

IL-18 inhibits osteoclast (OCL) formation in vitro independent of IFN-gamma production, and this was abolished by the addition of neutralizing antibodies to GM-CSF. We now establish that IL-18 was unable to inhibit OCL formation in cocultures using GM-CSF-deficient mice (GM-CSF -/-). Reciprocal cocultures using either wild-type osteoblasts with GM-CSF -/- spleen cells or GM-CSF -/- osteoblasts with wild-type spleen cells were examined. Wild-type spleen cells were required to elicit a response to IL-18 indicating that cells of splenic origin were the IL-18 target. As T cells comprise a large proportion of the spleen cell population, the role of T cells in osteoclastogenesis was examined. Total T cells were removed and repleted in various combinations. Addition of wild-type T cells to a GM-CSF -/- coculture restored IL-18 inhibition of osteoclastogenesis. Major subsets of T cells, CD4+ and CD8+, were also individually depleted. Addition of either CD4+ or CD8+ wild-type T cells restored IL-18 action in a GM-CSF -/- background, while IL-18 was ineffective when either CD4+ or CD8+ GM-CSF -/- T cells were added to a wild-type coculture. These results highlight the involvement of T cells in IL-18-induced OCL inhibition and provide evi...Continue Reading

References

Aug 1, 1990·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·C J RosenR A Adler
Nov 1, 1988·Endocrinology·N TakahashiT Suda
Jan 1, 1987·The American Journal of Pediatric Hematology/oncology·R ConsoliniE Bottone
Mar 1, 1984·Journal of Cell Science·T J ChambersN A Athanasou
Nov 1, 1994·Journal of Cellular Biochemistry·T J Martin, K W Ng
Jun 7, 1994·Proceedings of the National Academy of Sciences of the United States of America·E StanleyA R Dunn
Jan 1, 1993·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·F G HustmyerS C Manolagas
Oct 1, 1995·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·F J BuchinskyS Epstein
Jan 1, 1997·Journal of Cellular Biochemistry·P LiT Seshadri
Apr 15, 1997·Proceedings of the National Academy of Sciences of the United States of America·T YoshimotoK Nakanishi
May 19, 1997·Biochemical and Biophysical Research Communications·S MatsumotoM Kurimoto

❮ Previous
Next ❯

Citations

Oct 19, 2000·Arthritis and Rheumatism·E M Gravallese, S R Goldring
Jul 24, 2001·Arthritis and Rheumatism·I B McInnesF Y Liew
Nov 5, 1999·Biochemical and Biophysical Research Communications·N J HorwoodM T Gillespie
Feb 16, 2000·Biochemical and Biophysical Research Communications·C MenaaG D Roodman
Jan 1, 1997·Osteoporosis International : a Journal Established As Result of Cooperation Between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA·E Romas, T J Martin
Nov 12, 2005·Current Pain and Headache Reports·Iain B McInnes, J Alastair Gracie
Jul 31, 1999·Experimental Hematology·G D Roodman
Feb 19, 2000·Current Opinion in Immunology·S Akira
Oct 1, 1998·Cytokine & Growth Factor Reviews·M T Gillespie, N J Horwood
Sep 18, 2010·Nature Reviews. Immunology·Thirumala-Devi Kanneganti
Aug 31, 2011·Proceedings of the National Academy of Sciences of the United States of America·Rinke StienstraThirumala-Devi Kanneganti
Sep 11, 2008·The Journal of Biological Chemistry·Vicky KartsogiannisMatthew T Gillespie
May 10, 2000·Current Opinion in Rheumatology·S R Goldring, E M Gravallese
Jun 10, 2006·Current Opinion in Rheumatology·Sun-Kyeong Lee, Joseph Lorenzo
Apr 28, 2009·Current Opinion in Nephrology and Hypertension·Minnkyong Lee, Nicola C Partridge
May 16, 2007·Annals of the Rheumatic Diseases·Sheng-Ming DaiKusuki Nishioka
Mar 13, 2001·Annual Review of Immunology·K NakanishiH Okamura
Mar 6, 2013·Biochemia Medica·Janja ZupanJanja Marc
Jun 6, 2000·American Journal of Respiratory Cell and Molecular Biology·P G ArndtE Abraham
May 4, 2007·The Journal of Clinical Investigation·Ilona Gutcher, Burkhard Becher
Mar 23, 2000·The Journal of Clinical Investigation·Y OkadaC C Pilbeam
Nov 24, 1999·The Journal of Clinical Investigation·J M Dayer
Jan 12, 2005·Arthritis Research & Therapy·Iain B McInnesJ Alastair Gracie
May 3, 2008·Endocrine Reviews·Joseph LorenzoYongwon Choi
Aug 10, 2000·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·J M QuinnT J Martin
Oct 5, 2001·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·J M QuinnM T Gillespie
Jan 5, 2002·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Masanori KoideSakamuri V Reddy

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.