Inflammation Research[JOURNAL]

Sun 200 papers

SARS-CoV-2 drives upregulation of EpCAM in respiratory epithelial cells with hypercellular profile during severe COVID-19.

Araújo FP, Marques-Ferreira G, da Mata CPSM … +10 more , de Sousa Reis EV, Corrêa-Dias LC, Lopes-Ribeiro Á, Wilker-Teixeira C, Mendes GER, Peruhype-Magalhães V, Campi-Azevedo AC, Martins-Filho OA, Teixeira-Carvalho A, Coelho-Dos-Reis JGA

Inflamm Res · 2026 Jun · PMID 42323495 · Full text

BACKGROUND: At the end of 2019, severe acute respiratory syndrome (SARS) caused by the novel coronavirus SARS-CoV-2 emerged in China, representing one of the most significant global health threats of the twenty-first cen... BACKGROUND: At the end of 2019, severe acute respiratory syndrome (SARS) caused by the novel coronavirus SARS-CoV-2 emerged in China, representing one of the most significant global health threats of the twenty-first century. This study aimed to evaluate the phenotypic and cellular activation of epithelial cells in tracheal aspirate samples from patients with severe COVID-19. METHODS: A total of 48 samples were collected from 28 mechanically ventilated patients and analyzed using flow cytometry and conventional microscopy. RESULTS: The results revealed a high prevalence of basal, ciliary, undifferentiated cells, and pneumocytes displaying morphological abnormalities. Samples were classified into hypocellular and hypercellular profiles based on total cell counts. These profiles were associated with clinical outcomes, with hypercellular samples more frequently observed in patients who died. Hypercellular samples exhibited increased frequencies of basal, undifferentiated cells and pneumocytes, as well as a greater presence of CD45⁺ cells with elevated HLA-DR expression, indicating an influx of activated leukocytes and antigen-presenting cells. In contrast, hypocellular samples showed a higher proportion of CD45⁻PanCK⁺ cells, reflecting a predominance of epithelial cells. Hypercellular samples also demonstrated increased EpCAM⁺PanCK⁺ epithelial cells with more expression of Spike in the context of intense inflammation. ICAM-1 expression was elevated in CD45⁺ cells from hypercellular samples, while reduced in CD45⁻ cells. Finally, a superior connectivity was found for networks of correlations of hypercellular samples, especially amongst the compartments of cells expressing EpCAM. CONCLUSION: Together, these findings identify two distinct cellular profiles that may serve as prognostic indicators in severe COVID-19.

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ERK1/2 activation in anti-inflammatory effects and underlying signaling mechanisms.

Tao K, Xu L, Cheng C … +7 more , Yuan F, Yu Y, Zhang L, Li R, Xia R, Dong H, Wang X

Inflamm Res · 2026 Jun · PMID 42323492 · Publisher ↗

INTRODUCTION: ERK1/2 are core components of the MAPK signaling pathway and play a central role in the regulation of inflammation. Although ERK1/2 activation is well established for driving pro-inflammatory responses, acc... INTRODUCTION: ERK1/2 are core components of the MAPK signaling pathway and play a central role in the regulation of inflammation. Although ERK1/2 activation is well established for driving pro-inflammatory responses, accumulating evidence systematically summarized in this review demonstrates that ERK1/2 activation can also exert potent anti-inflammatory and pro-resolving effects. At the cellular level, ERK1/2 activation mediates anti-inflammatory regulation through multiple coordinated mechanisms: It promotes activation-induced cell death in T cells, drives macrophages and microglia toward anti-inflammatory phenotypes while fine-tuning their phagocytic activity, enhances efferocytosis of apoptotic cells by myeloid cells to drive inflammation resolution, inhibits dendritic cell maturation, and induces production of the key anti-inflammatory cytokine IL-10. At the molecular signaling pathway level, ERK1/2 suppresses pro-inflammatory NF-κB activity by stabilizing IκBα, directly interacting with NF-κB p65 subunit, or activating PPARγ in both immune cells and tissue-resident cells. In addition, ERK1/2 exerts anti-inflammatory effects through the Nrf2/HO-1 axis, which negatively regulates NF-κB. Further anti-inflammatory axes include the ERK1/2/CREB pathway and the FPR2/ERK1/2 pro-resolving signaling cascade. Other anti-inflammatory mechanisms include the ERK1/2/sCD14 axis that neutralizes LPS, ERK1/2-induced autophagy, and anti-inflammatory signaling triggered by diverse upstream regulators of ERK1/2. CONCLUSION: This review systematically consolidates the anti-inflammatory and pro-resolving effects of ERK1/2 activation and the underlying molecular mechanisms involved. These findings provide robust evidence that ERK1/2 activation can promote anti-inflammatory and inflammation-resolving responses and refine our understanding of the dual role of ERK1/2 as a "double-edged sword" in the regulation of inflammation.

Inflammation Research[JOURNAL]

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