\documentclass[10pt]{article}

\usepackage{fullpage}
\usepackage{setspace}
\usepackage{parskip}
\usepackage{titlesec}
\usepackage[section]{placeins}
\usepackage{xcolor}
\usepackage{breakcites}
\usepackage{lineno}
\usepackage{hyphenat}





\PassOptionsToPackage{hyphens}{url}
\usepackage[colorlinks = true,
            linkcolor = blue,
            urlcolor  = blue,
            citecolor = blue,
            anchorcolor = blue]{hyperref}
\usepackage{etoolbox}
\makeatletter
\patchcmd\@combinedblfloats{\box\@outputbox}{\unvbox\@outputbox}{}{%
  \errmessage{\noexpand\@combinedblfloats could not be patched}%
}%
\makeatother


\usepackage{natbib}




\renewenvironment{abstract}
  {{\bfseries\noindent{\abstractname}\par\nobreak}\footnotesize}
  {\bigskip}

\titlespacing{\section}{0pt}{*3}{*1}
\titlespacing{\subsection}{0pt}{*2}{*0.5}
\titlespacing{\subsubsection}{0pt}{*1.5}{0pt}


\usepackage{authblk}


\usepackage{graphicx}
\usepackage[space]{grffile}
\usepackage{latexsym}
\usepackage{textcomp}
\usepackage{longtable}
\usepackage{tabulary}
\usepackage{booktabs,array,multirow}
\usepackage{amsfonts,amsmath,amssymb}
\providecommand\citet{\cite}
\providecommand\citep{\cite}
\providecommand\citealt{\cite}
% You can conditionalize code for latexml or normal latex using this.
\newif\iflatexml\latexmlfalse
\providecommand{\tightlist}{\setlength{\itemsep}{0pt}\setlength{\parskip}{0pt}}%

\AtBeginDocument{\DeclareGraphicsExtensions{.pdf,.PDF,.eps,.EPS,.png,.PNG,.tif,.TIF,.jpg,.JPG,.jpeg,.JPEG}}

\usepackage[utf8]{inputenc}
\usepackage[greek,english]{babel}



\usepackage{float}








\begin{document}

\title{TRPV1 modulation of immune response in metastatic breast carcinoma:
Enhanced inflammatory response may hinder therapeutic potentials of
TRPV1 agonists}



\author[1]{Nuray Erin}%
\author[1]{Muhlis  Akman}%
\author[1]{Seren Haksever}%
\affil[1]{Akdeniz University}%


\vspace{-1em}



  
  \date{May 27, 2024}


\begingroup
\let\center\flushleft
\let\endcenter\endflushleft
\maketitle
\endgroup





\selectlanguage{english}
\begin{abstract}
Background and Purpose: The transient receptor potential vanilloid 1
(TRPV1) ion channels enhance cytotoxic immune response and may have
therapeutic potential in cancer treatment. Hence, we here determined how
activation of TRPV1 alters immune response of tumor-bearing mice.
Experimental Approach: Three different metastatic subset of 4T1 breast
carcinoma cells were used to induce tumors in Balb-c mice. Mix leukocyte
cultures (MLCs) using spleens and draining lymph nodes were prepared and
stimulated with various challenges. Effects of four different TRPV1
agonists, antagonist (AMG9810) and Gambogic Amide (GA), a TrkA agonist
that sensitizes TRPV1, on secreted levels of cytokines were determined.
Results: MLCs of tumor-bearing mice secreted markedly higher levels of
IL-6 and lower levels of IFN-\selectlanguage{greek}γ \selectlanguage{english}compared to control mice. We observed
differential effects of TRPV1 agonists, antagonist and GA in control and
mice bearing different subset of metastatic cells. TRPV1 and TrkA
agonists increased IFN--\selectlanguage{greek}γ \selectlanguage{english}and IL-17 secretion in control mice while they
markedly increased IL-6 secretion and suppressed IFN--\selectlanguage{greek}γ \selectlanguage{english}secretion in
tumor-bearing mice. Unexpectedly, AMG9810 acted as an inverse agonist
and did not antagonize the effects of TRPV1 agonists and GA did not
sensitize TRPV1 channels. Conclusions: Our results demonstrate
constitutive activity of TRPV1 in immune cells, suggesting cross
activation. Excessive chronic activation of TRPV1 in immune cells in the
presence of metastatic breast carcinoma may have detrimental effects.
Unexpected findings further document that a drug can have multiple
intrinsic activities and depending on surrounding factors can act on the
same receptor as an agonist, antagonist or inverse agonist.%
\end{abstract}%



\sloppy


\textbf{Hosted file}

\verb`manuscriptfinal submit BJP.docx`  available at \url{https://authorea.com/users/730839/articles/710272-trpv1-modulation-of-immune-response-in-metastatic-breast-carcinoma-enhanced-inflammatory-response-may-hinder-therapeutic-potentials-of-trpv1-agonists}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/Figure-1/Figure-1}

\end{center}
\end{figure}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/Figure-2/Figure-2}

\end{center}
\end{figure}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/Figure-3/Figure-3}

\end{center}
\end{figure}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/Figure-4/Figure-4}

\end{center}
\end{figure}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/Figure-5/Figure-5}

\end{center}
\end{figure}

\selectlanguage{english}
\FloatBarrier
\end{document}

