title: IGF-1 attenuates LPS induced pro-inflammatory cytokines expression in buffalo (Bubalus bubalis) granulosa cells.
abstract: Interaction between immune and endocrine system is a diverse process influencing cellular function and homeostasis in animals. Negative energy balance (NEB) during postpartum period in dairy animals usually suppresses these systems resulting in reproductive tract infection and infertility. These negative effects could be due to competition among endocrine and immune signaling pathways for common signaling molecules. The present work studied the effect of IGF-1 (50 ng/ml) on LPS (1 μg/ml) mediated pro-inflammatory cytokine expression (IL-1β, TNF-α, IL-6) and aromatase (CYP19A1) genes' expressions as well as proliferation of buffalo granulosa cells. The crosstalk between LPS and IGF-1 was also demonstrated through studying the activities of downstream signaling molecules (ERK1/2, Akt, NF-κB) by western blot and immunostaining. Gene expression analysis showed that IGF-1 significantly reduced the LPS induced expression of IL-1β, TNF-α and IL-6. LPS alone inhibited the CYP19A1 expression. However, co-treatment with IGF-1 reversed the inhibitory effect of LPS on CYP19A1 expression. LPS alone did not affect granulosa cell proliferation, but co-treatment with IGF-1, and IGF-1 alone enhanced the proliferation. Western blot results demonstrated that LPS caused the nuclear translocation of the NF-κB and increased the phosphorylation of ERK1/2 and Akt maximum at 15 min and 60 min, respectively. Nonetheless, co-treatment with IGF-1 delayed LPS induced phosphorylation of ERK1/2 (peak at 120 min), while promoting early Akt phosphorylation (peak at 5 min) with no effect on NF-κB translocation. Overall, IGF-1 delayed and reversed the effects of LPS, suggesting that high IGF-1 levels may combat infection during critical periods like NEB in postpartum dairy animals.
authors.affiliation: Molecular Endocrinology, Functional Genomics and Systems Biology Laboratory, Animal Biochemistry Division, National Dairy Research Institute, Karnal 132001, Haryana, India.
authors.forename: K
authors.initials: K
authors.lastname: Onnureddy
authors.affiliation: Molecular Endocrinology, Functional Genomics and Systems Biology Laboratory, Animal Biochemistry Division, National Dairy Research Institute, Karnal 132001, Haryana, India.
authors.lastname: Ravinder
authors.affiliation: Molecular Endocrinology, Functional Genomics and Systems Biology Laboratory, Animal Biochemistry Division, National Dairy Research Institute, Karnal 132001, Haryana, India.
authors.forename: Suneel Kumar
authors.initials: SK
authors.lastname: Onteru
authors.affiliation: Molecular Endocrinology, Functional Genomics and Systems Biology Laboratory, Animal Biochemistry Division, National Dairy Research Institute, Karnal 132001, Haryana, India. Electronic address: drdheer.singh@gmail.com.
authors.forename: Dheer
authors.initials: D
authors.lastname: Singh
mesh_terms: D000818:Animals; D001141:Aromatase / Q000235:genetics / Q000378:metabolism; D002020:Buffaloes / Q000235:genetics*; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D016207:Cytokines / Q000235:genetics* / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D006107:Granulosa Cells / Q000166:cytology / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism*; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008954:Models, Biological; D016328:NF-kappa B / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D021381:Protein Transport / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D016328:NF-kappa B; D007334:Insulin-Like Growth Factor I; D001141:Aromatase; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases
keywords: Buffalo; Crosstalk; Granulosa cells; IGF-1; LPS; Signaling