Polymerized Type I Collagen Downregulates STAT-1 Phosphorylation Through Engagement with LAIR-1 in Circulating Monocytes, Avoiding Long COVID

Olivares-Martínez, Elizabeth; Hernández-Ramírez, Diego Francisco; Núñez-Álvarez, Carlos Alberto; Meza-Sánchez, David Eduardo; Chapa, Mónica; Méndez-Flores, Silvia; Priego-Ranero, Ángel; Azamar-Llamas, Daniel; Olvera-Prado, Héctor; Rivas-Redonda, Kenia Ilian; Ochoa-Hein, Eric; López-Mosqueda, Luis Gerardo; Rojas-Castañeda, Estefano; Urbina-Terán, Said; Septién-Stute, Luis; Hernández-Gilsoul, Thierry; Aguilar-León, Diana; Torres-Villalobos, Gonzalo; Furuzawa-Carballeda, Janette

doi:10.3390/ijms26031018

Polymerized Type I Collagen Downregulates STAT-1 Phosphorylation Through Engagement with LAIR-1 in Circulating Monocytes, Avoiding Long COVID

Journal

International Journal of Molecular Sciences

ISSN

1422-0067

Publisher

MDPI

Date Issued

2025

Author(s)

Olivares-Martínez, Elizabeth

Hernández-Ramírez, Diego Francisco

Núñez-Álvarez, Carlos Alberto

Meza-Sánchez, David Eduardo

Chapa, Mónica

Méndez-Flores, Silvia

Priego-Ranero, Ángel

Azamar-Llamas, Daniel

Olvera-Prado, Héctor

Rivas-Redonda, Kenia Ilian

Ochoa-Hein, Eric

López-Mosqueda, Luis Gerardo

Rojas-Castañeda, Estefano

Urbina-Terán, Said

Septién-Stute, Luis

Hernández-Gilsoul, Thierry

Aguilar-León, Diana

Torres-Villalobos, Gonzalo

Furuzawa-Carballeda, Janette

Facultad de Ciencias de la Salud - CampCM

Type

text::journal::journal article

DOI

10.3390/ijms26031018

URL

https://scripta.up.edu.mx/handle/20.500.12552/11910

Abstract

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-γ, and M1 + LPS were analyzed by Western blot for NF-κB (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-γ-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. ©The authors ©MDPI.

License

Acceso Abierto

URL License

https://creativecommons.org/licenses/by-nc-sa/4.0/

How to cite

Olivares-Martínez, E., Hernández-Ramírez, D. F., Núñez-Álvarez, C. A., Meza-Sánchez, D. E., Chapa, M., Méndez-Flores, S., Priego-Ranero, Á., Azamar-Llamas, D., Olvera-Prado, H., Rivas-Redonda, K. I., Ochoa-Hein, E., López-Mosqueda, L. G., Rojas-Castañeda, E., Urbina-Terán, S., Septién-Stute, L., Hernández-Gilsoul, T., Aguilar-León, D., Torres-Villalobos, G., & Furuzawa-Carballeda, J. (2025). Polymerized Type I Collagen Downregulates STAT-1 Phosphorylation Through Engagement with LAIR-1 in Circulating Monocytes, Avoiding Long COVID. International Journal of Molecular Sciences, 26(3), 1018. https://doi.org/10.3390/ijms26031018