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The objective of this study was to assess fibrinogen (FIB) comodified with citrulline (CIT) and/or malondialdehyde-acetaldehyde (MAA) initiates macrophage-fibroblast interactions, leading to extracellular matrix (ECM) deposition that characterizes rheumatoid arthritis-associated interstitial lung disease (RA-ILD). Macrophages (Mϕ) were stimulated with native-FIB, FIB-CIT, FIB-MAA, or FIB-MAA-CIT. Supernatants (SNs) [Mϕ-SN (U-937-derived) or MϕP-SN (PBMC-derived)] or direct antigens were coincubated with human lung fibroblasts (HLFs). Gene expression was examined using RT-PCR. ECM deposition was quantified using immunohistochemistry and Western blot; cell signaling mechanisms were delineated. Platelet-derived growth factor (PDGF)-BB and TGF-β were measured in macrophage supernatants, and inhibition studies were performed using Su16f and SB431542, respectively. HLF gene expression of CD36 , COL6A3 , MMP-9 , MMP-10 , and MMP-12 was increased following stimulations with Mϕ-SN generated from modified FIB but not from direct antigens. HLF stimulated with MϕP-SN FIB-MAA-CIT derived from patients with RA-ILD resulted in 4- to 30-fold increases in COL6A3 and MMP12 expression; upregulation was greater in HLFs stimulated with MϕP-SN derived from RA-ILD versus controls. HLF exposure to Mϕ-SN FIB-MAA-CIT increased types I/VI collagen deposition versus all other Mϕ-SN groups and was greater than FIB-MAA-CIT stimulation. PDGF-BB and TGF-β signaling had the highest concentrations identified in Mϕ-SN FIB-MAA-CIT and MϕP-SN FIB-MAA-CIT , particularly from RA-ILD-derived cells. PDGF-BB and TGF-β inhibitors, alone and in combination, significantly reduced HLF-mediated ECM deposition from Mϕ-SN stimulations. These results show that comodified fibrinogen activates macrophages to produce PDGF-BB and TGF-β that promotes an aggressive HLF phenotype characterized by increased ECM deposition. These results suggest that targeting CIT and/or MAA modifications or downstream cellular signals could represent novel approaches to RA-ILD treatment. NEW & NOTEWORTHY This report demonstrates that fibrinogen simultaneously harboring two common posttranslational modifications activates macrophages to secrete platelet-derived growth factor (PDGF)-BB and transforming growth factor (TGF)-β. Resulting cross talk between activated macrophages and human lung fibroblasts leads to marked increases in extracellular matrix deposition. These protein modifications are abundant and colocalize in lung tissues from patients with rheumatoid arthritis-associated interstitial lung disease (RA-ILD), and the results suggest that agents targeting citrullination and/or malondialdehyde-acetaldehyde (MAA) adduct formation could represent novel therapeutic strategies.

Objectives: Race-related stress due to institutional racism is a pervasive reality for Black college students and contributes to poor mental health outcomes such as anxious arousal symptoms. One framework which may account for this association between chronic stress and anxious arousal symptoms is the reserve capacity model. This study investigated whether racial identity dimensions (racial centrality, public regard, private regard) and sense of belonging to the racial group contribute to this population's reserve capacity and buffer the association between institutional race-related stress and anxious arousal symptoms., Method: A sample of 134 Black college students completed racial identity, sense of belonging, and mental health questionnaires. These data were subjected to multiple regression analysis to assess the main and interactive effects of institutional race-related stress and dimensions of interest as predictors of anxious arousal symptoms., Results: The analysis indicated that higher levels of institutional race-related stress, racial centrality, and public regard were each associated with higher levels of anxious arousal while higher levels of private regard and sense of belonging were associated with lower levels of anxious arousal. Further investigation of interaction effects revealed that high levels of sense of belonging and low levels of public regard, respectively, buffered the association between institutional race-related stress and anxious arousal symptoms., Conclusions: These findings illustrate how certain racial identity dimensions and sense of belonging contribute to the reserve capacity of Black students experiencing institutional race-related stress. Results are further discussed in the context of extant literature on Black racial identity and the university context. (PsycInfo Database Record (c) 2025 APA, all rights reserved).