Skip to main content
Top
Published in: Journal of Neuroinflammation 1/2010

Open Access 01-12-2010 | Research

In vivo CHI3L1 (YKL-40) expression in astrocytes in acute and chronic neurological diseases

Authors: Dafna Bonneh-Barkay, Guoji Wang, Adam Starkey, Ronald L Hamilton, Clayton A Wiley

Published in: Journal of Neuroinflammation | Issue 1/2010

Login to get access

Abstract

Background

CHI3L1 (YKL-40) is up-regulated in a variety of inflammatory conditions and cancers. We have previously reported elevated CHI3L1 concentration in the cerebrospinal fluid (CSF) of human and non-human primates with lentiviral encephalitis and using immunohistochemistry showed that CHI3L1 was associated with astrocytes.

Methods

In the current study CHI3L1 transcription and expression were evaluated in a variety of acute and chronic human neurological diseases.

Results

ELISA revealed significant elevation of CHI3L1 in the CSF of multiple sclerosis (MS) patients as well as mild elevation with aging. In situ hybridization (ISH) showed CHI3L1 transcription mostly associated with reactive astrocytes, that was more pronounced in inflammatory conditions like lentiviral encephalitis and MS. Comparison of CHI3L1 expression in different stages of brain infarction showed that YKL40 was abundantly expressed in astrocytes during acute phases and diminished to low levels in chronic infarcts.

Conclusions

Taken together, these findings demonstrate that CHI3L1 is induced in astrocytes in a variety of neurological diseases but that it is most abundantly associated with astrocytes in regions of inflammatory cells.
Appendix
Available only for authorised users
Literature
1.
go back to reference Johansen JS: Studies on serum YKL-40 as a biomarker in diseases with inflammation, tissue remodelling, fibroses and cancer. Dan Med Bull. 2006, 53: 172-209.PubMed Johansen JS: Studies on serum YKL-40 as a biomarker in diseases with inflammation, tissue remodelling, fibroses and cancer. Dan Med Bull. 2006, 53: 172-209.PubMed
2.
go back to reference Jensen BV, Johansen JS, Price PA: High levels of serum HER-2/neu and YKL-40 independently reflect aggressiveness of metastatic breast cancer. Clin Cancer Res. 2003, 9: 4423-4434.PubMed Jensen BV, Johansen JS, Price PA: High levels of serum HER-2/neu and YKL-40 independently reflect aggressiveness of metastatic breast cancer. Clin Cancer Res. 2003, 9: 4423-4434.PubMed
3.
go back to reference Cintin C, Johansen JS, Christensen IJ, Price PA, Sorensen S, Nielsen HJ: High serum YKL-40 level after surgery for colorectal carcinoma is related to short survival. Cancer. 2002, 95: 267-274. 10.1002/cncr.10644.CrossRefPubMed Cintin C, Johansen JS, Christensen IJ, Price PA, Sorensen S, Nielsen HJ: High serum YKL-40 level after surgery for colorectal carcinoma is related to short survival. Cancer. 2002, 95: 267-274. 10.1002/cncr.10644.CrossRefPubMed
4.
go back to reference Brasso K, Christensen IJ, Johansen JS, Teisner B, Garnero P, Price PA, Iversen P: Prognostic value of PINP, bone alkaline phosphatase, CTX-I, and YKL-40 in patients with metastatic prostate carcinoma. Prostate. 2006, 66: 503-513. 10.1002/pros.20311.CrossRefPubMed Brasso K, Christensen IJ, Johansen JS, Teisner B, Garnero P, Price PA, Iversen P: Prognostic value of PINP, bone alkaline phosphatase, CTX-I, and YKL-40 in patients with metastatic prostate carcinoma. Prostate. 2006, 66: 503-513. 10.1002/pros.20311.CrossRefPubMed
5.
go back to reference Hormigo A, Gu B, Karimi S, Riedel E, Panageas KS, Edgar MA, Tanwar MK, Rao JS, Fleisher M, DeAngelis LM, Holland EC: YKL-40 and matrix metalloproteinase-9 as potential serum biomarkers for patients with high-grade gliomas. Clin Cancer Res. 2006, 12: 5698-5704. 10.1158/1078-0432.CCR-06-0181.CrossRefPubMed Hormigo A, Gu B, Karimi S, Riedel E, Panageas KS, Edgar MA, Tanwar MK, Rao JS, Fleisher M, DeAngelis LM, Holland EC: YKL-40 and matrix metalloproteinase-9 as potential serum biomarkers for patients with high-grade gliomas. Clin Cancer Res. 2006, 12: 5698-5704. 10.1158/1078-0432.CCR-06-0181.CrossRefPubMed
6.
go back to reference Rand V, Prebble E, Ridley L, Howard M, Wei W, Brundler MA, Fee BE, Riggins GJ, Coyle B, Grundy RG: Investigation of chromosome 1q reveals differential expression of members of the S100 family in clinical subgroups of intracranial paediatric ependymoma. Br J Cancer. 2008, 99: 1136-1143. 10.1038/sj.bjc.6604651.PubMedCentralCrossRefPubMed Rand V, Prebble E, Ridley L, Howard M, Wei W, Brundler MA, Fee BE, Riggins GJ, Coyle B, Grundy RG: Investigation of chromosome 1q reveals differential expression of members of the S100 family in clinical subgroups of intracranial paediatric ependymoma. Br J Cancer. 2008, 99: 1136-1143. 10.1038/sj.bjc.6604651.PubMedCentralCrossRefPubMed
7.
go back to reference Letuve S, Kozhich A, Arouche N, Grandsaigne M, Reed J, Dombret MC, Kiener PA, Aubier M, Coyle AJ, Pretolani M: YKL-40 is elevated in patients with chronic obstructive pulmonary disease and activates alveolar macrophages. J Immunol. 2008, 181: 5167-5173.CrossRefPubMed Letuve S, Kozhich A, Arouche N, Grandsaigne M, Reed J, Dombret MC, Kiener PA, Aubier M, Coyle AJ, Pretolani M: YKL-40 is elevated in patients with chronic obstructive pulmonary disease and activates alveolar macrophages. J Immunol. 2008, 181: 5167-5173.CrossRefPubMed
8.
go back to reference Chupp GL, Lee CG, Jarjour N, Shim YM, Holm CT, He S, Dziura JD, Reed J, Coyle AJ, Kiener P, Cullen M, Grandsaigne M, Dombret MC, Aubier M, Pretolani M, Elias JA: A chitinase-like protein in the lung and circulation of patients with severe asthma. N Engl J Med. 2007, 357: 2016-2027. 10.1056/NEJMoa073600.CrossRefPubMed Chupp GL, Lee CG, Jarjour N, Shim YM, Holm CT, He S, Dziura JD, Reed J, Coyle AJ, Kiener P, Cullen M, Grandsaigne M, Dombret MC, Aubier M, Pretolani M, Elias JA: A chitinase-like protein in the lung and circulation of patients with severe asthma. N Engl J Med. 2007, 357: 2016-2027. 10.1056/NEJMoa073600.CrossRefPubMed
9.
go back to reference Ober C, Tan Z, Sun Y, Possick JD, Pan L, Nicolae R, Radford S, Parry RR, Heinzmann A, Deichmann KA, Lester LA, Gern JE, Lemanske RF, Nicolae DL, Elias JA, Chupp GL: Effect of variation in CHI3L1 on serum YKL-40 level, risk of asthma, and lung function. N Engl J Med. 2008, 358: 1682-1691. 10.1056/NEJMoa0708801.PubMedCentralCrossRefPubMed Ober C, Tan Z, Sun Y, Possick JD, Pan L, Nicolae R, Radford S, Parry RR, Heinzmann A, Deichmann KA, Lester LA, Gern JE, Lemanske RF, Nicolae DL, Elias JA, Chupp GL: Effect of variation in CHI3L1 on serum YKL-40 level, risk of asthma, and lung function. N Engl J Med. 2008, 358: 1682-1691. 10.1056/NEJMoa0708801.PubMedCentralCrossRefPubMed
10.
go back to reference Kuepper M, Bratke K, Virchow JC: Chitinase-like protein and asthma. N Engl J Med. 2008, 358: 1073-1075. 10.1056/NEJMc073406. author reply 1075CrossRefPubMed Kuepper M, Bratke K, Virchow JC: Chitinase-like protein and asthma. N Engl J Med. 2008, 358: 1073-1075. 10.1056/NEJMc073406. author reply 1075CrossRefPubMed
11.
go back to reference Bonneh-Barkay D, Bissel SJ, Wang G, Fish KN, Nicholl GC, Darko SW, Medina-Flores R, Murphey-Corb M, Rajakumar PA, Nyaundi J, Mellors JW, Bowser R, Wiley CA: YKL-40, a marker of simian immunodeficiency virus encephalitis, modulates the biological activity of basic fibroblast growth factor. Am J Pathol. 2008, 173: 130-143. 10.2353/ajpath.2008.080045.PubMedCentralCrossRefPubMed Bonneh-Barkay D, Bissel SJ, Wang G, Fish KN, Nicholl GC, Darko SW, Medina-Flores R, Murphey-Corb M, Rajakumar PA, Nyaundi J, Mellors JW, Bowser R, Wiley CA: YKL-40, a marker of simian immunodeficiency virus encephalitis, modulates the biological activity of basic fibroblast growth factor. Am J Pathol. 2008, 173: 130-143. 10.2353/ajpath.2008.080045.PubMedCentralCrossRefPubMed
12.
go back to reference Lee CG, Hartl D, Lee GR, Koller B, Matsuura H, Da Silva CA, Sohn MH, Cohn L, Homer RJ, Kozhich AA, Humbles A, Kearley J, Coyle A, Chupp G, Reed J, Flavell RA, Elias JA: Role of breast regression protein 39 (BRP-39)/chitinase 3-like-1 in Th2 and IL-13-induced tissue responses and apoptosis. J Exp Med. 2009, 206: 1149-1166. 10.1084/jem.20081271.PubMedCentralCrossRefPubMed Lee CG, Hartl D, Lee GR, Koller B, Matsuura H, Da Silva CA, Sohn MH, Cohn L, Homer RJ, Kozhich AA, Humbles A, Kearley J, Coyle A, Chupp G, Reed J, Flavell RA, Elias JA: Role of breast regression protein 39 (BRP-39)/chitinase 3-like-1 in Th2 and IL-13-induced tissue responses and apoptosis. J Exp Med. 2009, 206: 1149-1166. 10.1084/jem.20081271.PubMedCentralCrossRefPubMed
13.
go back to reference Chung C, Tallerico T, Seeman P: Schizophrenia hippocampus has elevated expression of chondrex glycoprotein gene. Synapse. 2003, 50: 29-34. 10.1002/syn.10228.CrossRefPubMed Chung C, Tallerico T, Seeman P: Schizophrenia hippocampus has elevated expression of chondrex glycoprotein gene. Synapse. 2003, 50: 29-34. 10.1002/syn.10228.CrossRefPubMed
14.
go back to reference Garbett K, Ebert PJ, Mitchell A, Lintas C, Manzi B, Mirnics K, Persico AM: Immune transcriptome alterations in the temporal cortex of subjects with autism. Neurobiol Dis. 2008, 30: 303-311. 10.1016/j.nbd.2008.01.012.PubMedCentralCrossRefPubMed Garbett K, Ebert PJ, Mitchell A, Lintas C, Manzi B, Mirnics K, Persico AM: Immune transcriptome alterations in the temporal cortex of subjects with autism. Neurobiol Dis. 2008, 30: 303-311. 10.1016/j.nbd.2008.01.012.PubMedCentralCrossRefPubMed
15.
go back to reference Colton CA, Mott RT, Sharpe H, Xu Q, Van Nostrand WE, Vitek MP: Expression profiles for macrophage alternative activation genes in AD and in mouse models of AD. J Neuroinflammation. 2006, 3: 27-10.1186/1742-2094-3-27.PubMedCentralCrossRefPubMed Colton CA, Mott RT, Sharpe H, Xu Q, Van Nostrand WE, Vitek MP: Expression profiles for macrophage alternative activation genes in AD and in mouse models of AD. J Neuroinflammation. 2006, 3: 27-10.1186/1742-2094-3-27.PubMedCentralCrossRefPubMed
16.
go back to reference Ostergaard C, Johansen JS, Benfield T, Price PA, Lundgren JD: YKL-40 is elevated in cerebrospinal fluid from patients with purulent meningitis. Clin Diagn Lab Immunol. 2002, 9: 598-604.PubMedCentralPubMed Ostergaard C, Johansen JS, Benfield T, Price PA, Lundgren JD: YKL-40 is elevated in cerebrospinal fluid from patients with purulent meningitis. Clin Diagn Lab Immunol. 2002, 9: 598-604.PubMedCentralPubMed
17.
go back to reference Mullett SJ, Hamilton RL, Hinkle DA: DJ-1 immunoreactivity in human brain astrocytes is dependent on infarct presence and infarct age. Neuropathology. 2009, 29: 125-131. 10.1111/j.1440-1789.2008.00955.x.CrossRefPubMed Mullett SJ, Hamilton RL, Hinkle DA: DJ-1 immunoreactivity in human brain astrocytes is dependent on infarct presence and infarct age. Neuropathology. 2009, 29: 125-131. 10.1111/j.1440-1789.2008.00955.x.CrossRefPubMed
18.
go back to reference Arion D, Unger T, Lewis DA, Levitt P, Mirnics K: Molecular evidence for increased expression of genes related to immune and chaperone function in the prefrontal cortex in schizophrenia. Biol Psychiatry. 2007, 62: 711-721. 10.1016/j.biopsych.2006.12.021.PubMedCentralCrossRefPubMed Arion D, Unger T, Lewis DA, Levitt P, Mirnics K: Molecular evidence for increased expression of genes related to immune and chaperone function in the prefrontal cortex in schizophrenia. Biol Psychiatry. 2007, 62: 711-721. 10.1016/j.biopsych.2006.12.021.PubMedCentralCrossRefPubMed
19.
go back to reference Yang MS, Morris DW, Donohoe G, Kenny E, O'Dushalaine CT, Schwaiger S, Nangle JM, Clarke S, Scully P, Quinn J, Meagher D, Baldwin P, Crumlish N, O'Callaghan E, Waddington JL, Gill M, Corvin A: Chitinase-3-like 1 (CHI3L1) gene and schizophrenia: genetic association and a potential functional mechanism. Biol Psychiatry. 2008, 64: 98-103. 10.1016/j.biopsych.2007.12.012.CrossRefPubMed Yang MS, Morris DW, Donohoe G, Kenny E, O'Dushalaine CT, Schwaiger S, Nangle JM, Clarke S, Scully P, Quinn J, Meagher D, Baldwin P, Crumlish N, O'Callaghan E, Waddington JL, Gill M, Corvin A: Chitinase-3-like 1 (CHI3L1) gene and schizophrenia: genetic association and a potential functional mechanism. Biol Psychiatry. 2008, 64: 98-103. 10.1016/j.biopsych.2007.12.012.CrossRefPubMed
20.
go back to reference Zhao X, Tang R, Gao B, Shi Y, Zhou J, Guo S, Zhang J, Wang Y, Tang W, Meng J, Li S, Wang H, Ma G, Lin C, Xiao Y, Feng G, Lin Z, Zhu S, Xing Y, Sang H, St Clair D, He L: Functional variants in the promoter region of Chitinase 3-like 1 (CHI3L1) and susceptibility to schizophrenia. Am J Hum Genet. 2007, 80: 12-18. 10.1086/510438.PubMedCentralCrossRefPubMed Zhao X, Tang R, Gao B, Shi Y, Zhou J, Guo S, Zhang J, Wang Y, Tang W, Meng J, Li S, Wang H, Ma G, Lin C, Xiao Y, Feng G, Lin Z, Zhu S, Xing Y, Sang H, St Clair D, He L: Functional variants in the promoter region of Chitinase 3-like 1 (CHI3L1) and susceptibility to schizophrenia. Am J Hum Genet. 2007, 80: 12-18. 10.1086/510438.PubMedCentralCrossRefPubMed
21.
go back to reference Yamada K, Hattori E, Iwayama Y, Toyota T, Ohnishi T, Iwata Y, Tsuchiya KJ, Sugihara G, Kikuchi M, Okazaki Y, Yoshikawa T: Failure to confirm genetic association of the CHI3L1 gene with schizophrenia in Japanese and Chinese populations. Am J Med Genet B Neuropsychiatr Genet. 2008, 150B (4): 508-14.CrossRef Yamada K, Hattori E, Iwayama Y, Toyota T, Ohnishi T, Iwata Y, Tsuchiya KJ, Sugihara G, Kikuchi M, Okazaki Y, Yoshikawa T: Failure to confirm genetic association of the CHI3L1 gene with schizophrenia in Japanese and Chinese populations. Am J Med Genet B Neuropsychiatr Genet. 2008, 150B (4): 508-14.CrossRef
22.
go back to reference Shao R, Hamel K, Petersen L, Cao QJ, Arenas RB, Bigelow C, Bentley B, Yan W: YKL-40, a secreted glycoprotein, promotes tumor angiogenesis. Oncogene. 2009, 17: 4456-68. 10.1038/onc.2009.292.CrossRef Shao R, Hamel K, Petersen L, Cao QJ, Arenas RB, Bigelow C, Bentley B, Yan W: YKL-40, a secreted glycoprotein, promotes tumor angiogenesis. Oncogene. 2009, 17: 4456-68. 10.1038/onc.2009.292.CrossRef
Metadata
Title
In vivo CHI3L1 (YKL-40) expression in astrocytes in acute and chronic neurological diseases
Authors
Dafna Bonneh-Barkay
Guoji Wang
Adam Starkey
Ronald L Hamilton
Clayton A Wiley
Publication date
01-12-2010
Publisher
BioMed Central
Published in
Journal of Neuroinflammation / Issue 1/2010
Electronic ISSN: 1742-2094
DOI
https://doi.org/10.1186/1742-2094-7-34

Other articles of this Issue 1/2010

Journal of Neuroinflammation 1/2010 Go to the issue