000129320 001__ 129320
000129320 005__ 20240104111812.0
000129320 0247_ $$2doi$$a10.3389/fimmu.2019.00801
000129320 0248_ $$2sideral$$a111404
000129320 037__ $$aART-2019-111404
000129320 041__ $$aeng
000129320 100__ $$0(orcid)0000-0002-7277-4318$$aMoreno-Martínez, Laura$$uUniversidad de Zaragoza
000129320 245__ $$aCirculating Cytokines Could Not Be Good Prognostic Biomarkers in a Mouse Model of Amyotrophic Lateral Sclerosis.
000129320 260__ $$c2019
000129320 5060_ $$aAccess copy available to the general public$$fUnrestricted
000129320 5203_ $$aBackground: There is growing evidence of the role of inflammation in Amyotrophic Lateral Sclerosis (ALS) during the last decade. Although the origin of ALS remains unknown, multiple potential inflammatory biomarkers have been described in ALS patients and murine models of this disease to explain the progressive motor neuron loss and muscle atrophy. However, the results remain controversial. To shed light on this issue, we aimed to identify novel biomarkers of inflammation that can influence disease progression and survival in serial blood samples from transgenic SOD1G93A mice, a model of ALS.
Methods: A cytokine array assay was performed to analyze protein expression of 97 cytokines in plasma samples from wildtype controls and transgenic SOD1G93A mice at asymptomatic stage. Subsequently, serial plasma samples were obtained from SOD1G93A mice at early symptomatic, symptomatic and terminal stages to monitor cytokine levels during disease progression through immunoassays. Comparisons of means of quantifiable cytokines between short-and long-lived mice were analyzed by unrelated t-test or Mann-Whitney U-test. Relationships between cytokines levels and survival time were assessed using Pearson's correlation analysis and Kaplan-Meier analysis.
Results: A total of 16 cytokines (6Ckine, ALK-1, CD30 L, eotaxin-1, galectin-1, GITR, IL-2, IL-6, IL-10, IL-13, IL-17B R, MIP-1a, MIP-3ß, RANKL, TROY, and VEGF-D) were found dysregulated in transgenic SOD1G93A mice at asymptomatic stage compared with age-matched controls. Immunoassays of serial samples revealed positive expression of ALK-1, GITR and IL-17B R at P60 and P90 in mice with shorter survival. In addition, eotaxin-1 and galectin-1 levels were significantly increased at terminal stage in SOD1G93A mice that showed shorter survival time. Finally, levels of eotaxin-1, galectin-1, IL-2, IL-6, MIP-1a, and TROY at P90 or endpoint negatively correlated with the longevity of transgenic mice.
Conclusions: We demonstrated in the SOD1G93A model of ALS that increased levels of several cytokines were associated with a shorter lifespan. However, their role as prognostic biomarkers is unclear as their expression was very variable depending on both the disease stage and the subject. Nevertheless, cytokines may be potential therapeutic targets.
000129320 536__ $$9info:eu-repo/grantAgreement/ES/DGA-FEDER/Construyendo Europa desde Aragón$$9info:eu-repo/grantAgreement/ES/DGA/FSE$$9info:eu-repo/grantAgreement/ES/FIS/PI17-00949
000129320 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttp://creativecommons.org/licenses/by/3.0/es/
000129320 590__ $$a5.085$$b2019
000129320 591__ $$aIMMUNOLOGY$$b38 / 158 = 0.241$$c2019$$dQ1$$eT1
000129320 592__ $$a2.116$$b2019
000129320 593__ $$aImmunology and Allergy$$c2019$$dQ1
000129320 593__ $$aImmunology$$c2019$$dQ1
000129320 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000129320 700__ $$0(orcid)0000-0002-7955-7164$$ade la Torre, Miriam$$uUniversidad de Zaragoza
000129320 700__ $$0(orcid)0000-0002-7243-1737$$aToivonen, Janne M.$$uUniversidad de Zaragoza
000129320 700__ $$0(orcid)0000-0001-5740-0185$$aZaragoza, Pilar$$uUniversidad de Zaragoza
000129320 700__ $$aGarcía-Redondo, Alberto
000129320 700__ $$0(orcid)0000-0001-5193-7782$$aCalvo, Ana C.$$uUniversidad de Zaragoza
000129320 700__ $$0(orcid)0000-0001-5687-6704$$aOsta, Rosario$$uUniversidad de Zaragoza
000129320 7102_ $$11001$$2420$$aUniversidad de Zaragoza$$bDpto. Anatom.,Embri.Genét.Ani.$$cÁrea Genética
000129320 773__ $$g10 (2019), 801$$pFront. immunol.$$tFrontiers in Immunology$$x1664-3224
000129320 8564_ $$s1629262$$uhttps://zaguan.unizar.es/record/129320/files/texto_completo.pdf$$yVersión publicada
000129320 8564_ $$s2146317$$uhttps://zaguan.unizar.es/record/129320/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000129320 909CO $$ooai:zaguan.unizar.es:129320$$particulos$$pdriver
000129320 951__ $$a2024-01-04-11:02:57
000129320 980__ $$aARTICLE