Objectives: Calgranulins S100A8 and S100A9 are common in renal stones and they are up-regulated in both urinary exosomes and kidneys of stone patients. Renal sources and important regulators for S100A8 and S100A9 in nephrolithiasis were explored in this study.
Materials And Methods: We identified S100A8 and S100A9 abundance in various renal cells by searching the Single Cell Type Atlas. Macrophages were polarized from human myeloid leukemia mononuclear cells. Human proximal renal tubular epithelial cells (HK-2) were stimulated with calcium oxalate monohydrate (COM). Coculture experiments involving HK-2 cells and macrophages were conducted. qPCR, Western blotting, ELISA, and immunofluorescence were used for detecting interleukin 6 (IL6), S100A8, and S100A9.
Results: The Single Cell Type Atlas showed that S100A8 and S100A9 in human kidneys primarily originated from macrophages. M1 was the predominant macrophage type expressing S100A8 and S100A9. Direct culture with COM did not affect the expression of these two calgranulins in M1 macrophages but coculture with COM-treated HK-2 cells did. COM could promote HK-2 cells to secrete IL6. IL6 could up-regulate S100A8 and S100A9 expression in macrophages of M1 type. In addition, 0.5 μM SC144 (a kind of IL6 inhibitor) significantly prevented COM-treated HK-2 cells from up-regulating S100A8 and S100A9 expression in macrophages of M1 type.
Conclusion: M1-polarized macrophages were the predominant cell type expressing S100A8 and S100A9 in the kidneys of nephrolithiasis patients. CaOx crystals can promote renal tubular epithelial cells to secrete IL6 to up-regulate S100A8 and S100A9 expression in macrophages of M1 type.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10083839 | PMC |
| http://dx.doi.org/10.22038/IJBMS.2023.69202.15080 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
S100A8/A9 innate immune signaling as a distinct mechanism driving progression of smoking-related breast cancers.
Oncogene
January 2025
Department of Pathology, University of California, San Diego, La Jolla, USA.
Smoking plays an underappreciated role in breast cancer progression, increasing recurrence and mortality in patients. Here, we show that S100A8/A9 innate immune signaling is a molecular mechanism that identifies smoking-related breast cancers and underlies their enhanced malignancy. In contrast to acute exposure, chronic nicotine increased tumorigenicity and reprogrammed breast cancer cells to express innate immune response genes.
View Article and Find Full Text PDFAn S100A8/A9 neutralizing antibody potently ameliorates contact hypersensitivity and atopic dermatitis symptoms.
J Invest Dermatol
January 2025
Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan. Electronic address:
Contact hypersensitivity (CHS) and atopic dermatitis (AD) are pervasive inflammatory skin diseases with similar symptoms, and the global prevalence of both conditions is steadily rising. Many compounds and biotics have been developed to target molecules critical to the etiology or pathogenesis of CHS and AD. However, such molecules are sometimes ineffective or lose potency over the therapeutic course.
View Article and Find Full Text PDFMetagenome-informed metaproteomics of the human gut microbiome, host, and dietary exposome uncovers signatures of health and inflammatory bowel disease.
Cell
January 2025
Department of Systems Immunology, Weizmann Institute of Science, Rehovot, Israel; Division of Microbiome & Cancer, DKFZ, Heidelberg, Germany. Electronic address:
Host-microbiome-dietary interactions play crucial roles in regulating human health, yet their direct functional assessment remains challenging. We adopted metagenome-informed metaproteomics (MIM), in mice and humans, to non-invasively explore species-level microbiome-host interactions during commensal and pathogen colonization, nutritional modification, and antibiotic-induced perturbation. Simultaneously, fecal MIM accurately characterized the nutritional exposure landscape in multiple clinical and dietary contexts.
View Article and Find Full Text PDFPlasma S100A8/A9 level predicts response to immune checkpoint inhibitors in patients with advanced non-small cell lung cancer.
Sci Rep
January 2025
Department of Allergy and Respiratory Medicine, Okayama University Hospital, 2-5-1 Shikata-cho, Kita-ku, Okayama, Japan.
Blood-based predictive markers for the efficacy of immune checkpoint inhibitors (ICIs) have not yet been established. We investigated the association of the plasma level of S100A8/A9 with the efficacy of immunotherapy. We evaluated patients with unresectable stage III/IV or recurrent non-small cell lung cancer (NSCLC) who were treated with ICIs at Okayama University Hospital.
View Article and Find Full Text PDFMonocytes generated by interleukin-6-treated human hematopoietic stem and progenitor cells secrete calprotectin that inhibits erythropoiesis.
iScience
January 2025
INSERM U1287, Université Paris-Saclay, Gustave Roussy Cancer Center, Villejuif, France.
Elevated circulating levels of calprotectin (CAL), the S100A8/A9 heterodimer, are biomarkers of severe systemic inflammation. Here, we investigate the effects of CAL on early human hematopoiesis. CAL demonstrates limited impact on gene expression in stem and progenitor cells, in contrast with interleukin-6 (IL6), which promotes the expression of the and genes in hematopoietic progenitors and the generation of monocytes that release CAL.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!