Polymerized Type I Collagen Downregulates STAT-1 Phosphorylation Through Engagement with LAIR-1 in Circulating Monocytes, Avoiding Long COVID
Por:
Olivares-Martínez, E, Hernández-Ramírez, DF, Núñez-alvarez, CA, Meza-Sánchez, DE, Chapa, M, Méndez-Flores, S, Priego-Ranero, A, Azamar-Llamas, D, Olvera-Prado, H, Rivas-Redonda, KI, Ochoa-Hein, E, López-Mosqueda, LG, Rojas-Castañeda, E, Urbina-Terán, S, Septién-Stute, L, Hernández-Gilsoul, T, Aguilar-León, D, Torres-Villalobos, G, Furuzawa-Carballeda, J
Publicada:
1 feb 2025
Resumen:
The intramuscular administration of polymerized type I collagen (PTIC) for adult symptomatic COVID-19 outpatients downregulated hyperinflammation and improved symptoms. We inferred that LAIR1 is a potential receptor for PTIC. Thus, a binding assay and surface plasmon resonance binding assay were performed to estimate the affinity of the interaction between LAIR1 and PTIC. M1 macrophages derived from THP-1 cells were cultured with 2-10% PTIC for 24 h. Lysates from PTIC-treated THP-1 cells, macrophage-like cells (MLCs), M1, M1 + IFN-gamma, and M1 + LPS were analyzed by Western blot for NF-kappa B (p65), p38, STAT1, and pSTAT1 (tyrosine701). Serum cytokine levels and monocyte LAIR1 expressions (Mo1 and Mo2) were analyzed by luminometry and flow cytometry in symptomatic COVID-19 outpatients on PTIC treatment. PTIC-bound LAIR1 had a similar affinity to collagen in M1 macrophages. It downregulated pSTAT1 in IFN-gamma-induced M1. COVID-19 patients under PTIC treatment showed a significant decrease in Mo1 percentages and cytokines (IP-10/MIF/eotaxin/IL-8/IL-1RA/M-CSF) associated with STAT1 and an increase in the Mo2 subset. The inflammatory mediators and Mo1 downregulation were related to better oxygen saturation and decreased dyspnea, chest pain, cough, and chronic fatigue syndrome in the acute and long-term phase of infection. PTIC is an agonist of LAIR1 and downregulates STAT-1 phosphorylation. PTIC could be relevant for treating STAT1-mediated inflammatory diseases, including COVID-19 and long COVID.
Filiaciones:
Olivares-Martínez, E:
Inst Nacl Ciencias Med & Nutr Salvador Zubiran, Dept Immunol & Rheumatol, Mexico City 14080, Mexico
Hernández-Ramírez, DF:
Inst Nacl Ciencias Med & Nutr Salvador Zubiran, Dept Immunol & Rheumatol, Mexico City 14080, Mexico
Meza-Sánchez, DE:
Univ Nacl Autonoma Mexico, Inst Nacl Ciencias Med & Nutr Salvador Zubiran, Red Apoyo Invest, Coordinac Invest Cient, Mexico City 14080, Mexico
Chapa, M:
Inst Nacl Ciencias Med & Nutr Salvador Zubiran, Dept Radiol, Mexico City 14080, Mexico
Méndez-Flores, S:
Inst Nacl Ciencias Med & Nutr Salvador Zubiran, Dept Dermatol, Mexico City, Mexico
Priego-Ranero, A:
Inst Nacl Ciencias Med & Nutr Salvador Zubiran, Dept Internal Med, Mexico City 14080, Mexico
Azamar-Llamas, D:
Inst Nacl Ciencias Med & Nutr Salvador Zubiran, Dept Internal Med, Mexico City 14080, Mexico
Olvera-Prado, H:
Inst Nacl Ciencias Med & Nutr Salvador Zubiran, Dept Anesthesiol, Mexico City 14080, Mexico
Rivas-Redonda, KI:
Inst Nacl Ciencias Med & Nutr Salvador Zubiran, Dept Immunol & Rheumatol, Mexico City 14080, Mexico
Ochoa-Hein, E:
Inst Nacl Ciencias Med & Nutr Salvador Zubiran, Dept Hosp Epidemiol, Mexico City 14080, Mexico
López-Mosqueda, LG:
Inst Nacl Ciencias Med & Nutr Salvador Zubiran, Dept Immunol & Rheumatol, Mexico City 14080, Mexico
Rojas-Castañeda, E:
Inst Nacl Ciencias Med & Nutr Salvador Zubiran, Dept Internal Med, Mexico City 14080, Mexico
Urbina-Terán, S:
Inst Nacl Ciencias Med & Nutr Salvador Zubiran, Emergency Dept, Mexico City 14080, Mexico
Septién-Stute, L:
Inst Nacl Ciencias Med & Nutr Salvador Zubiran, Dept Pneumol, Mexico City 14080, Mexico
Hernández-Gilsoul, T:
Inst Nacl Ciencias Med & Nutr Salvador Zubiran, Emergency Dept, Mexico City 14080, Mexico
Aguilar-León, D:
Inst Nacl Ciencias Med & Nutr Salvador Zubiran, Dept Pathol, Mexico City 14080, Mexico
Torres-Villalobos, G:
Inst Nacl Ciencias Med & Nutr Salvador Zubiran, Dept Expt Surg, Mexico City 14080, Mexico
Inst Nacl Ciencias Med & Nutr Salvador Zubiran, Dept Surg, Mexico City 14080, Mexico
Furuzawa-Carballeda, J:
Inst Nacl Ciencias Med & Nutr Salvador Zubiran, Dept Expt Surg, Mexico City 14080, Mexico
Inst Nacl Ciencias Med & Nutr Salvador Zubiran, Dept Surg, Mexico City 14080, Mexico
Univ Panamer, Sch Med, Mexico City 14080, Mexico
gold, All Open Access; Gold Open Access
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